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Auteur David G. AMARAL |
Documents disponibles écrits par cet auteur (34)
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Further characterization of autoantibodies to GABAergic neurons in the central nervous system produced by a subset of children with autism / Sharifia WILLS in Molecular Autism, (April 2011)
[article]
Titre : Further characterization of autoantibodies to GABAergic neurons in the central nervous system produced by a subset of children with autism Type de document : Texte imprimé et/ou numérique Auteurs : Sharifia WILLS, Auteur ; Christy C. ROSSI, Auteur ; Jeffrey BENNETT, Auteur ; Veronica M. CERDENO, Auteur ; Paul ASHWOOD, Auteur ; David G. AMARAL, Auteur ; Judy VAN DE WATER, Auteur Année de publication : 2011 Article en page(s) : 15 p. Langues : Anglais (eng) Index. décimale : PER Périodiques Résumé : Background
Autism is a neurodevelopmental disorder characterized by impairments in social interaction and deficits in verbal and nonverbal communication, together with the presence of repetitive behaviors or a limited repertoire of activities and interests. The causes of autism are currently unclear. In a previous study, we determined that 21% of children with autism have plasma autoantibodies that are immunoreactive with a population of neurons in the cerebellum that appear to be Golgi cells, which are GABAergic interneurons.
Methods
We have extended this analysis by examining plasma immunoreactivity in the remainder of the brain. To determine cell specificity, double-labeling studies that included one of the calcium-binding proteins that are commonly colocalized in GABAergic neurons (calbindin, parvalbumin or calretinin) were also carried out to determine which GABAergic neurons are immunoreactive. Coronal sections through the rostrocaudal extent of the macaque monkey brain were reacted with plasma from each of seven individuals with autism who had previously demonstrated positive Golgi cell staining, as well as six negative controls. In addition, brain sections from adult male mice were similarly examined.
Results
In each case, specific staining was observed for neurons that had the morphological appearance of interneurons. By double-labeling sections with plasma and with antibodies directed against γ-aminobutyric acid (GABA), we determined that all autoantibody-positive neurons were GABAergic. However, not all GABAergic neurons were autoantibody-positive. Calbindin was colabeled in several of the autoantibody-labeled cells, while parvalbumin colabeling was less frequently observed. Autoantibody-positive cells rarely expressed calretinin. Sections from the mouse brain processed similarly to the primate sections also demonstrated immunoreactivity to interneurons distributed throughout the neocortex and many subcortical regions. Some cell populations stained in the primate (such as the Golgi neurons in the cerebellum) were not as robustly immunoreactive in the mouse brain.
Conclusions
These results suggest that the earlier report of autoantibody immunoreactivity to specific cells in the cerebellum extend to other regions of the brain. Further, these findings confirm the autoantibody-targeted cells to be a subpopulation of GABAergic interneurons. The potential impact of these autoantibodies on GABAergic disruption with respect to the etiology of autism is discussed herein.En ligne : http://dx.doi.org/10.1186/2040-2392-2-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=131
in Molecular Autism > (April 2011) . - 15 p.[article] Further characterization of autoantibodies to GABAergic neurons in the central nervous system produced by a subset of children with autism [Texte imprimé et/ou numérique] / Sharifia WILLS, Auteur ; Christy C. ROSSI, Auteur ; Jeffrey BENNETT, Auteur ; Veronica M. CERDENO, Auteur ; Paul ASHWOOD, Auteur ; David G. AMARAL, Auteur ; Judy VAN DE WATER, Auteur . - 2011 . - 15 p.
Langues : Anglais (eng)
in Molecular Autism > (April 2011) . - 15 p.
Index. décimale : PER Périodiques Résumé : Background
Autism is a neurodevelopmental disorder characterized by impairments in social interaction and deficits in verbal and nonverbal communication, together with the presence of repetitive behaviors or a limited repertoire of activities and interests. The causes of autism are currently unclear. In a previous study, we determined that 21% of children with autism have plasma autoantibodies that are immunoreactive with a population of neurons in the cerebellum that appear to be Golgi cells, which are GABAergic interneurons.
Methods
We have extended this analysis by examining plasma immunoreactivity in the remainder of the brain. To determine cell specificity, double-labeling studies that included one of the calcium-binding proteins that are commonly colocalized in GABAergic neurons (calbindin, parvalbumin or calretinin) were also carried out to determine which GABAergic neurons are immunoreactive. Coronal sections through the rostrocaudal extent of the macaque monkey brain were reacted with plasma from each of seven individuals with autism who had previously demonstrated positive Golgi cell staining, as well as six negative controls. In addition, brain sections from adult male mice were similarly examined.
Results
In each case, specific staining was observed for neurons that had the morphological appearance of interneurons. By double-labeling sections with plasma and with antibodies directed against γ-aminobutyric acid (GABA), we determined that all autoantibody-positive neurons were GABAergic. However, not all GABAergic neurons were autoantibody-positive. Calbindin was colabeled in several of the autoantibody-labeled cells, while parvalbumin colabeling was less frequently observed. Autoantibody-positive cells rarely expressed calretinin. Sections from the mouse brain processed similarly to the primate sections also demonstrated immunoreactivity to interneurons distributed throughout the neocortex and many subcortical regions. Some cell populations stained in the primate (such as the Golgi neurons in the cerebellum) were not as robustly immunoreactive in the mouse brain.
Conclusions
These results suggest that the earlier report of autoantibody immunoreactivity to specific cells in the cerebellum extend to other regions of the brain. Further, these findings confirm the autoantibody-targeted cells to be a subpopulation of GABAergic interneurons. The potential impact of these autoantibodies on GABAergic disruption with respect to the etiology of autism is discussed herein.En ligne : http://dx.doi.org/10.1186/2040-2392-2-5 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=131 Gaps in Current Autism Research: The Thoughts of the Autism Research Editorial Board and Associate Editors / David G. AMARAL in Autism Research, 12-5 (May 2019)
[article]
Titre : Gaps in Current Autism Research: The Thoughts of the Autism Research Editorial Board and Associate Editors Type de document : Texte imprimé et/ou numérique Auteurs : David G. AMARAL, Auteur ; George M. ANDERSON, Auteur ; A. BAILEY, Auteur ; Raphael BERNIER, Auteur ; Somer L. BISHOP, Auteur ; Gene J. BLATT, Auteur ; Ricardo CANAL-BEDIA, Auteur ; Tony CHARMAN, Auteur ; G. DAWSON, Auteur ; P. J. DE VRIES, Auteur ; Emanuel DICICCO-BLOOM, Auteur ; Cheryl DISSANAYAKE, Auteur ; Y. KAMIO, Auteur ; R. KANA, Auteur ; N. Z. KHAN, Auteur ; A. KNOLL, Auteur ; F. KOOY, Auteur ; J. LAINHART, Auteur ; P. LEVITT, Auteur ; K. LOVELAND, Auteur ; N. MINSHEW, Auteur ; R. A. MUELLER, Auteur ; D. MURPHY, Auteur ; Peter C. MUNDY, Auteur ; S. PALENCIA, Auteur ; J. PINTO-MARTIN, Auteur ; A. RATTAZZI, Auteur ; S. ROGERS, Auteur ; W. L. STONE, Auteur ; S. J. WEBB, Auteur ; Andrew J. O. WHITEHOUSE, Auteur Article en page(s) : p.700-714 Langues : Anglais (eng) Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.2101 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=397
in Autism Research > 12-5 (May 2019) . - p.700-714[article] Gaps in Current Autism Research: The Thoughts of the Autism Research Editorial Board and Associate Editors [Texte imprimé et/ou numérique] / David G. AMARAL, Auteur ; George M. ANDERSON, Auteur ; A. BAILEY, Auteur ; Raphael BERNIER, Auteur ; Somer L. BISHOP, Auteur ; Gene J. BLATT, Auteur ; Ricardo CANAL-BEDIA, Auteur ; Tony CHARMAN, Auteur ; G. DAWSON, Auteur ; P. J. DE VRIES, Auteur ; Emanuel DICICCO-BLOOM, Auteur ; Cheryl DISSANAYAKE, Auteur ; Y. KAMIO, Auteur ; R. KANA, Auteur ; N. Z. KHAN, Auteur ; A. KNOLL, Auteur ; F. KOOY, Auteur ; J. LAINHART, Auteur ; P. LEVITT, Auteur ; K. LOVELAND, Auteur ; N. MINSHEW, Auteur ; R. A. MUELLER, Auteur ; D. MURPHY, Auteur ; Peter C. MUNDY, Auteur ; S. PALENCIA, Auteur ; J. PINTO-MARTIN, Auteur ; A. RATTAZZI, Auteur ; S. ROGERS, Auteur ; W. L. STONE, Auteur ; S. J. WEBB, Auteur ; Andrew J. O. WHITEHOUSE, Auteur . - p.700-714.
Langues : Anglais (eng)
in Autism Research > 12-5 (May 2019) . - p.700-714
Index. décimale : PER Périodiques En ligne : http://dx.doi.org/10.1002/aur.2101 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=397 Identifying autism symptom severity trajectories across childhood / Einat WAIZBARD-BARTOV in Autism Research, 15-4 (April 2022)
[article]
Titre : Identifying autism symptom severity trajectories across childhood Type de document : Texte imprimé et/ou numérique Auteurs : Einat WAIZBARD-BARTOV, Auteur ; Emilio FERRER, Auteur ; Brianna HEATH, Auteur ; Sally J. ROGERS, Auteur ; Christine W. NORDAHL, Auteur ; Marjorie SOLOMON, Auteur ; David G. AMARAL, Auteur Article en page(s) : p.687-701 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/diagnosis Autistic Disorder/diagnosis/epidemiology Child Child, Preschool Family Female Humans Individuality Male Parents Ados autism spectrum disorder calibrated severity scores longitudinal severity change sex differences Index. décimale : PER Périodiques Résumé : An individual's autism symptom severity level can change across childhood. The prevalence and direction of change, however, are still not well understood. Nor are the characteristics of children that experience change. Symptom severity trajectories were evaluated from early to middle childhood (approximately ages 3-11) for 182 autistic children. Symptom severity change was evaluated using individual change scores and the Reliable Change Index. Fifty-one percent of participants experienced symptom severity change: 27% of children decreased in severity, 24% increased and 49% were stable. Symptom severity decreases were more common during early childhood. Severity increases occurred at both early and middle childhood but increase in social affect severity was especially prominent during middle childhood. Most children experienced significant change during only one period and remained stable during the other. Girls decreased more and increased less in symptom severity than boys. Children that increased in severity decreased in adaptive functioning across childhood. Exploratory analyses indicated that a decrease in severity was associated with higher parental education level and older parental age at the time of the child's birth. Conversely, increase in autism severity was associated with lower parental education level and younger parental age at the child's birth. These findings extend recent observations that symptom severity change is more likely than previously appreciated. An understanding of the role of both biological and sociodemographic factors in determining a child's symptom trajectory may factor into future decisions on allocation and type of interventions distributed to young autistic children. LAY SUMMARY: We studied whether a child's autism severity changed from initial diagnosis until middle childhood (ages 3-11). We found that 27% of the children decreased in severity, 24% increased and the rest stayed the same. Symptom severity decreases were more common during early childhood while severity increases were more prominent during middle childhood. We also found that girls were more likely to decrease than boys. Whether a child decreased or increased is related, in part, to parental characteristics. En ligne : https://dx.doi.org/10.1002/aur.2674 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=473
in Autism Research > 15-4 (April 2022) . - p.687-701[article] Identifying autism symptom severity trajectories across childhood [Texte imprimé et/ou numérique] / Einat WAIZBARD-BARTOV, Auteur ; Emilio FERRER, Auteur ; Brianna HEATH, Auteur ; Sally J. ROGERS, Auteur ; Christine W. NORDAHL, Auteur ; Marjorie SOLOMON, Auteur ; David G. AMARAL, Auteur . - p.687-701.
Langues : Anglais (eng)
in Autism Research > 15-4 (April 2022) . - p.687-701
Mots-clés : Autism Spectrum Disorder/diagnosis Autistic Disorder/diagnosis/epidemiology Child Child, Preschool Family Female Humans Individuality Male Parents Ados autism spectrum disorder calibrated severity scores longitudinal severity change sex differences Index. décimale : PER Périodiques Résumé : An individual's autism symptom severity level can change across childhood. The prevalence and direction of change, however, are still not well understood. Nor are the characteristics of children that experience change. Symptom severity trajectories were evaluated from early to middle childhood (approximately ages 3-11) for 182 autistic children. Symptom severity change was evaluated using individual change scores and the Reliable Change Index. Fifty-one percent of participants experienced symptom severity change: 27% of children decreased in severity, 24% increased and 49% were stable. Symptom severity decreases were more common during early childhood. Severity increases occurred at both early and middle childhood but increase in social affect severity was especially prominent during middle childhood. Most children experienced significant change during only one period and remained stable during the other. Girls decreased more and increased less in symptom severity than boys. Children that increased in severity decreased in adaptive functioning across childhood. Exploratory analyses indicated that a decrease in severity was associated with higher parental education level and older parental age at the time of the child's birth. Conversely, increase in autism severity was associated with lower parental education level and younger parental age at the child's birth. These findings extend recent observations that symptom severity change is more likely than previously appreciated. An understanding of the role of both biological and sociodemographic factors in determining a child's symptom trajectory may factor into future decisions on allocation and type of interventions distributed to young autistic children. LAY SUMMARY: We studied whether a child's autism severity changed from initial diagnosis until middle childhood (ages 3-11). We found that 27% of the children decreased in severity, 24% increased and the rest stayed the same. Symptom severity decreases were more common during early childhood while severity increases were more prominent during middle childhood. We also found that girls were more likely to decrease than boys. Whether a child decreased or increased is related, in part, to parental characteristics. En ligne : https://dx.doi.org/10.1002/aur.2674 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=473 In pursuit of neurophenotypes: The consequences of having autism and a big brain / David G. AMARAL in Autism Research, 10-5 (May 2017)
[article]
Titre : In pursuit of neurophenotypes: The consequences of having autism and a big brain Type de document : Texte imprimé et/ou numérique Auteurs : David G. AMARAL, Auteur ; Deana LI, Auteur ; Lauren LIBERO, Auteur ; Marjorie SOLOMON, Auteur ; Judy VAN DE WATER, Auteur ; Ann MASTERGEORGE, Auteur ; Letitia NAIGLES, Auteur ; Sally J ROGERS, Auteur ; Christine W. NORDAHL, Auteur Article en page(s) : p.711-722 Langues : Anglais (eng) Mots-clés : brain development magnetic resonance imaging megalencephaly phenotype subtypes Index. décimale : PER Périodiques Résumé : A consensus has emerged that despite common core features, autism spectrum disorder (ASD) has multiple etiologies and various genetic and biological characteristics. The fact that there are likely to be subtypes of ASD has complicated attempts to develop effective therapies. The UC Davis MIND Institute Autism Phenome Project is a longitudinal, multidisciplinary analysis of children with autism and age-matched typically developing controls; nearly 400 families are participating in this study. The overarching goal is to gather sufficient biological, medical, and behavioral data to allow definition of clinically meaningful subtypes of ASD. One reasonable hypothesis is that different subtypes of autism will demonstrate different patterns of altered brain organization or development i.e., different neurophenotypes. In this Commentary, we discuss one neurophenotype that is defined by megalencephaly, or having brain size that is large and disproportionate to body size. We have found that 15% of the boys with autism demonstrate this neurophenotype, though it is far less common in girls. We review behavioral and medical characteristics of the large-brained group of boys with autism in comparison to those with typically sized brains. While brain size in typically developing individuals is positively correlated with cognitive function, the children with autism and larger brains have more severe disabilities and poorer prognosis. This research indicates that phenotyping in autism, like genotyping, requires a very substantial cohort of subjects. Moreover, since brain and behavior relationships may emerge at different times during development, this effort highlights the need for longitudinal analyses to carry out meaningful phenotyping. En ligne : http://dx.doi.org/10.1002/aur.1755 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=307
in Autism Research > 10-5 (May 2017) . - p.711-722[article] In pursuit of neurophenotypes: The consequences of having autism and a big brain [Texte imprimé et/ou numérique] / David G. AMARAL, Auteur ; Deana LI, Auteur ; Lauren LIBERO, Auteur ; Marjorie SOLOMON, Auteur ; Judy VAN DE WATER, Auteur ; Ann MASTERGEORGE, Auteur ; Letitia NAIGLES, Auteur ; Sally J ROGERS, Auteur ; Christine W. NORDAHL, Auteur . - p.711-722.
Langues : Anglais (eng)
in Autism Research > 10-5 (May 2017) . - p.711-722
Mots-clés : brain development magnetic resonance imaging megalencephaly phenotype subtypes Index. décimale : PER Périodiques Résumé : A consensus has emerged that despite common core features, autism spectrum disorder (ASD) has multiple etiologies and various genetic and biological characteristics. The fact that there are likely to be subtypes of ASD has complicated attempts to develop effective therapies. The UC Davis MIND Institute Autism Phenome Project is a longitudinal, multidisciplinary analysis of children with autism and age-matched typically developing controls; nearly 400 families are participating in this study. The overarching goal is to gather sufficient biological, medical, and behavioral data to allow definition of clinically meaningful subtypes of ASD. One reasonable hypothesis is that different subtypes of autism will demonstrate different patterns of altered brain organization or development i.e., different neurophenotypes. In this Commentary, we discuss one neurophenotype that is defined by megalencephaly, or having brain size that is large and disproportionate to body size. We have found that 15% of the boys with autism demonstrate this neurophenotype, though it is far less common in girls. We review behavioral and medical characteristics of the large-brained group of boys with autism in comparison to those with typically sized brains. While brain size in typically developing individuals is positively correlated with cognitive function, the children with autism and larger brains have more severe disabilities and poorer prognosis. This research indicates that phenotyping in autism, like genotyping, requires a very substantial cohort of subjects. Moreover, since brain and behavior relationships may emerge at different times during development, this effort highlights the need for longitudinal analyses to carry out meaningful phenotyping. En ligne : http://dx.doi.org/10.1002/aur.1755 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=307 Increased Surface Area, but not Cortical Thickness, in a Subset of Young Boys With Autism Spectrum Disorder / Haruhisa OHTA in Autism Research, 9-2 (February 2016)
[article]
Titre : Increased Surface Area, but not Cortical Thickness, in a Subset of Young Boys With Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : Haruhisa OHTA, Auteur ; Christine W. NORDAHL, Auteur ; Ana-Maria IOSIF, Auteur ; Aaron LEE, Auteur ; Sally J ROGERS, Auteur ; David G. AMARAL, Auteur Article en page(s) : p.232-248 Langues : Anglais (eng) Mots-clés : cortical thickness surface area gray matter volume megalencephaly autism spectrum disorder FreeSurfer Index. décimale : PER Périodiques Résumé : The Autism Phenome Project is the largest, single site, longitudinal magnetic resonance imaging (MRI) study of young children with autism spectrum disorder (ASD). Previous analyses from this cohort have shown that the children with autism have a total brain volume at time 1 (?3 years of age) that is 6% larger than typically developing (TD) children. This finding is driven primarily by 15% of the boys with ASD that have disproportionate megalencephaly (ASD-DM) or brain size that is 1.5 standard deviations above what would be expected for the child's height. In the current study, cerebral cortical grey matter volume, thickness, and surface area were assayed from MRI scans of 112, 3-year-old boys with ASD and 50 age-matched TD boys. The boys with ASD-DM (n?=?17) were analyzed separately from the boys with normal brain size (ASD-N, n?=?95). Previous studies of cortical thickness and surface area for ASD children in this age range have come to diametrically different conclusions concerning the significance of cortical thickness vs. surface area. Current analyses indicate that cortical thickness was comparable across the ASD and TD groups. However, surface area was significantly greater in the ASD group compared to the TD group. This result was driven largely by the children with ASD-DM. Even in the ASD-DM group, not all cortical regions demonstrated increased surface area. These results provide strong evidence that the early cortical overgrowth associated with ASD is due primarily to increased surface area and not to increased cortical thickness. En ligne : http://dx.doi.org/10.1002/aur.1520 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=282
in Autism Research > 9-2 (February 2016) . - p.232-248[article] Increased Surface Area, but not Cortical Thickness, in a Subset of Young Boys With Autism Spectrum Disorder [Texte imprimé et/ou numérique] / Haruhisa OHTA, Auteur ; Christine W. NORDAHL, Auteur ; Ana-Maria IOSIF, Auteur ; Aaron LEE, Auteur ; Sally J ROGERS, Auteur ; David G. AMARAL, Auteur . - p.232-248.
Langues : Anglais (eng)
in Autism Research > 9-2 (February 2016) . - p.232-248
Mots-clés : cortical thickness surface area gray matter volume megalencephaly autism spectrum disorder FreeSurfer Index. décimale : PER Périodiques Résumé : The Autism Phenome Project is the largest, single site, longitudinal magnetic resonance imaging (MRI) study of young children with autism spectrum disorder (ASD). Previous analyses from this cohort have shown that the children with autism have a total brain volume at time 1 (?3 years of age) that is 6% larger than typically developing (TD) children. This finding is driven primarily by 15% of the boys with ASD that have disproportionate megalencephaly (ASD-DM) or brain size that is 1.5 standard deviations above what would be expected for the child's height. In the current study, cerebral cortical grey matter volume, thickness, and surface area were assayed from MRI scans of 112, 3-year-old boys with ASD and 50 age-matched TD boys. The boys with ASD-DM (n?=?17) were analyzed separately from the boys with normal brain size (ASD-N, n?=?95). Previous studies of cortical thickness and surface area for ASD children in this age range have come to diametrically different conclusions concerning the significance of cortical thickness vs. surface area. Current analyses indicate that cortical thickness was comparable across the ASD and TD groups. However, surface area was significantly greater in the ASD group compared to the TD group. This result was driven largely by the children with ASD-DM. Even in the ASD-DM group, not all cortical regions demonstrated increased surface area. These results provide strong evidence that the early cortical overgrowth associated with ASD is due primarily to increased surface area and not to increased cortical thickness. En ligne : http://dx.doi.org/10.1002/aur.1520 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=282 Introduction to commentary by Laurent Mottron and responses / David G. AMARAL in Autism Research, 14-10 (October 2021)
PermalinkLanguage in Autism Research: Accurate and Respectful / David G. AMARAL in Autism Research, 16-1 (January 2023)
PermalinkMacrocephaly and megalencephaly in autism spectrum disorder / Lauren E. LIBERO
PermalinkA Metabolomics Approach to Screening for Autism Risk in the Children's Autism Metabolome Project / Alan M. SMITH in Autism Research, 13-8 (August 2020)
PermalinkMethods for acquiring MRI data in children with autism spectrum disorder and intellectual impairment without the use of sedation / Christine W. NORDAHL in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)
PermalinkNeural correlates of language variability in preschool-aged boys with autism spectrum disorder / Letitia R. NAIGLES in Autism Research, 10-6 (June 2017)
PermalinkNeuropathology of Autism Spectrum Disorders: Postmortem Studies / Cynthia M. SCHUMANN
PermalinkNonhuman Primate Models for Autism Spectrum Disorders / Melissa D. BAUMAN
PermalinkNonhuman Primate Models of Autism / Melissa D. BAUMAN
PermalinkOffering to Share: How to Put Heads Together in Autism Neuroimaging / Matthew K. BELMONTE in Journal of Autism and Developmental Disorders, 38-1 (January 2008)
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