Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects / C. LINTAS in Journal of Neurodevelopmental Disorders, 8-1 (December 2016)  

Public ISBD [article]  inJournal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.18 Titre : Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects Type de document : Texte imprimé et/ou numérique Auteurs : C. LINTAS, Auteur ; R. SACCO, Auteur ; A. M. PERSICO, Auteur Article en page(s) : p.18 Langues : Anglais (eng) Mots-clés : Autism  DNA methylation  Epigenetics  Post-mortem brains  Reelin Index. décimale : PER Périodiques Résumé : BACKGROUND: Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. METHODS: In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. RESULTS: ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5' region of the RELN gene promoter, spanning from -458 to -223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3' promoter region, spanning from -222 to +1 bp. The most upstream promoter region (-458 to -364 bp) is methylated only in ASD brains, while the most downstream region (-131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. CONCLUSIONS: The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression. En ligne : http://dx.doi.org/10.1186/s11689-016-9151-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348 [article] Differential methylation at the RELN gene promoter in temporal cortex from autistic and typically developing post-puberal subjects [Texte imprimé et/ou numérique] / C. LINTAS, Auteur ; R. SACCO, Auteur ; A. M. PERSICO, Auteur . - p.18. Langues : Anglais (eng) in Journal of Neurodevelopmental Disorders > 8-1 (December 2016) . - p.18 Mots-clés : Autism  DNA methylation  Epigenetics  Post-mortem brains  Reelin Index. décimale : PER Périodiques Résumé : BACKGROUND: Reelin plays a pivotal role in neurodevelopment and in post-natal synaptic plasticity and has been implicated in the pathogenesis of autism spectrum disorder (ASD). The reelin (RELN) gene expression is significantly decreased in ASD, both in the brain and peripherally. Methylation at the RELN gene promoter is largely triggered at puberty, and hypermethylation has been found in post-mortem brains of schizophrenic and bipolar patients. METHODS: In this study, we assessed RELN gene methylation status in post-mortem temporocortical tissue samples (BA41/42 or 22) of six pairs of post-puberal individuals with ASD and typically developing subjects, matched for sex (male:female, M:F = 5:1), age, and post-mortem interval. RESULTS: ASD patients display a significantly higher number of methylated CpG islands and heavier methylation in the 5' region of the RELN gene promoter, spanning from -458 to -223 bp, whereas controls have more methylated CpG positions and greater extent of methylation at the 3' promoter region, spanning from -222 to +1 bp. The most upstream promoter region (-458 to -364 bp) is methylated only in ASD brains, while the most downstream region (-131 to +1 bp) is methylated exclusively in control brains. Within this general framework, three different methylation patterns are discernible, each correlated with different extents of reduction in reelin gene expression among ASD individuals compared to controls. CONCLUSIONS: The methylation pattern is different in ASD and control post-mortem brains. ASD-specific CpG positions, located in the most upstream gene promoter region, may exert a functional role potentially conferring ASD risk by blunting RELN gene expression. En ligne : http://dx.doi.org/10.1186/s11689-016-9151-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=348

Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-site Sample of Individuals with Autism Spectrum Disorder / J. TILLMANN in Journal of Autism and Developmental Disorders, 48-7 (July 2018)  

Public ISBD [article]  inJournal of Autism and Developmental Disorders > 48-7 (July 2018) . - p.2490-2505 Titre : Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-site Sample of Individuals with Autism Spectrum Disorder Type de document : Texte imprimé et/ou numérique Auteurs : J. TILLMANN, Auteur ; K. ASHWOOD, Auteur ; M. ABSOUD, Auteur ; Sven BÖLTE, Auteur ; Frédérique BONNET-BRILHAULT, Auteur ; Jan K. BUITELAAR, Auteur ; Sara CALDERONI, Auteur ; R. CALVO, Auteur ; Ricardo CANAL-BEDIA, Auteur ; Roberto CANITANO, Auteur ; Annelies A. DE BILDT, Auteur ; Marie GOMOT, Auteur ; P. J. HOEKSTRA, Auteur ; A. KAALE, Auteur ; H. MCCONACHIE, Auteur ; D. G. MURPHY, Auteur ; A. NARZISI, Auteur ; I. OOSTERLING, Auteur ; M. PEJOVIC-MILOVANCEVIC, Auteur ; A. M. PERSICO, Auteur ; O. PUIG, Auteur ; H. ROEYERS, Auteur ; Nanda N. ROMMELSE, Auteur ; R. SACCO, Auteur ; V. SCANDURRA, Auteur ; A. C. STANFIELD, Auteur ; E. ZANDER, Auteur ; Tony CHARMAN, Auteur Article en page(s) : p.2490-2505 Langues : Anglais (eng) Mots-clés : Age  Autism Spectrum Disorder  Phenotype  Sex  Symptom severity Index. décimale : PER Périodiques Résumé : Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology. En ligne : http://dx.doi.org/10.1007/s10803-018-3510-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=367 [article] Evaluating Sex and Age Differences in ADI-R and ADOS Scores in a Large European Multi-site Sample of Individuals with Autism Spectrum Disorder [Texte imprimé et/ou numérique] / J. TILLMANN, Auteur ; K. ASHWOOD, Auteur ; M. ABSOUD, Auteur ; Sven BÖLTE, Auteur ; Frédérique BONNET-BRILHAULT, Auteur ; Jan K. BUITELAAR, Auteur ; Sara CALDERONI, Auteur ; R. CALVO, Auteur ; Ricardo CANAL-BEDIA, Auteur ; Roberto CANITANO, Auteur ; Annelies A. DE BILDT, Auteur ; Marie GOMOT, Auteur ; P. J. HOEKSTRA, Auteur ; A. KAALE, Auteur ; H. MCCONACHIE, Auteur ; D. G. MURPHY, Auteur ; A. NARZISI, Auteur ; I. OOSTERLING, Auteur ; M. PEJOVIC-MILOVANCEVIC, Auteur ; A. M. PERSICO, Auteur ; O. PUIG, Auteur ; H. ROEYERS, Auteur ; Nanda N. ROMMELSE, Auteur ; R. SACCO, Auteur ; V. SCANDURRA, Auteur ; A. C. STANFIELD, Auteur ; E. ZANDER, Auteur ; Tony CHARMAN, Auteur . - p.2490-2505. Langues : Anglais (eng) in Journal of Autism and Developmental Disorders > 48-7 (July 2018) . - p.2490-2505 Mots-clés : Age  Autism Spectrum Disorder  Phenotype  Sex  Symptom severity Index. décimale : PER Périodiques Résumé : Research on sex-related differences in Autism Spectrum Disorder (ASD) has been impeded by small samples. We pooled 28 datasets from 18 sites across nine European countries to examine sex differences in the ASD phenotype on the ADI-R (376 females, 1763 males) and ADOS (233 females, 1187 males). On the ADI-R, early childhood restricted and repetitive behaviours were lower in females than males, alongside comparable levels of social interaction and communication difficulties in females and males. Current ADI-R and ADOS scores showed no sex differences for ASD severity. There were lower socio-communicative symptoms in older compared to younger individuals. This large European ASD sample adds to the literature on sex and age variations of ASD symptomatology. En ligne : http://dx.doi.org/10.1007/s10803-018-3510-4 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=367

Gut mobilization improves behavioral symptoms and modulates urinary p-cresol in chronically constipated autistic children: A prospective study / L. TURRIZIANI in Autism Research, 15-1 (January 2022)  

Public ISBD [article]  inAutism Research > 15-1 (January 2022) . - p.56-69 Titre : Gut mobilization improves behavioral symptoms and modulates urinary p-cresol in chronically constipated autistic children: A prospective study Type de document : Texte imprimé et/ou numérique Auteurs : L. TURRIZIANI, Auteur ; A. RICCIARDELLO, Auteur ; F. CUCINOTTA, Auteur ; F. BELLOMO, Auteur ; G. TURTURO, Auteur ; M. BONCODDO, Auteur ; S. MIRABELLI, Auteur ; M. L. SCATTONI, Auteur ; M. ROSSI, Auteur ; A. M. PERSICO, Auteur Article en page(s) : p.56-69 Langues : Anglais (eng) Mots-clés : Autism Spectrum Disorder/complications  Autistic Disorder/complications  Behavioral Symptoms  Child  Child, Preschool  Constipation/complications  Cresols/urine  Gastrointestinal Microbiome  Gastrointestinal Motility  Humans  Prospective Studies  4-cresol  anxiety  autism  autism spectrum disorder  biomarkers  constipation  microbiota Index. décimale : PER Périodiques Résumé : Chronic constipation is common among children with ASD and is associated with more severe hyperactivity, anxiety, irritability, and repetitive behaviors. Young autistic children with chronic constipation display higher urinary, and foecal concentrations of p-cresol, an aromatic compound produced by gut bacteria, known to negatively affect brain function. Acute p-cresol administration to BTBR mice enhances anxiety, hyperactivity and stereotypic behaviors, while blunting social interaction. This study was undertaken to prospectively assess the behavioral effects of gut mobilization in young autistic children with chronic constipation, and to verify their possible correlation with urinary p-cresol. To this aim, 21 chronically constipated autistic children 2-8?years old were evaluated before (T0), 1?month (T1), and 6?months (T2) after intestinal mobilization, recording Bristol stool scale scores, urinary p-cresol concentrations, and behavioral scores for social interaction deficits, stereotypic behaviors, anxiety, and hyperactivity. Gut mobilization yielded a progressive and highly significant decrease in all behavioral symptoms over the 6-month study period. Urinary p-cresol levels displayed variable trends not significantly correlated with changes in behavioral parameters, mainly increasing at T1 and decreasing at T2. These results support gut mobilization as a simple strategy to ameliorate ASD symptoms, as well as comorbid anxiety and hyperactivity, in chronically constipated children. Variation in p-cresol absorption seemingly provides limited contributions, if any, to these behavioral changes. Further research will be needed to address the relative role of reduced abdominal discomfort following mobilization, as compared to specific modifications in microbiome composition and in gut bacteria-derived neuroactive compounds. En ligne : http://dx.doi.org/10.1002/aur.2639 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450 [article] Gut mobilization improves behavioral symptoms and modulates urinary p-cresol in chronically constipated autistic children: A prospective study [Texte imprimé et/ou numérique] / L. TURRIZIANI, Auteur ; A. RICCIARDELLO, Auteur ; F. CUCINOTTA, Auteur ; F. BELLOMO, Auteur ; G. TURTURO, Auteur ; M. BONCODDO, Auteur ; S. MIRABELLI, Auteur ; M. L. SCATTONI, Auteur ; M. ROSSI, Auteur ; A. M. PERSICO, Auteur . - p.56-69. Langues : Anglais (eng) in Autism Research > 15-1 (January 2022) . - p.56-69 Mots-clés : Autism Spectrum Disorder/complications  Autistic Disorder/complications  Behavioral Symptoms  Child  Child, Preschool  Constipation/complications  Cresols/urine  Gastrointestinal Microbiome  Gastrointestinal Motility  Humans  Prospective Studies  4-cresol  anxiety  autism  autism spectrum disorder  biomarkers  constipation  microbiota Index. décimale : PER Périodiques Résumé : Chronic constipation is common among children with ASD and is associated with more severe hyperactivity, anxiety, irritability, and repetitive behaviors. Young autistic children with chronic constipation display higher urinary, and foecal concentrations of p-cresol, an aromatic compound produced by gut bacteria, known to negatively affect brain function. Acute p-cresol administration to BTBR mice enhances anxiety, hyperactivity and stereotypic behaviors, while blunting social interaction. This study was undertaken to prospectively assess the behavioral effects of gut mobilization in young autistic children with chronic constipation, and to verify their possible correlation with urinary p-cresol. To this aim, 21 chronically constipated autistic children 2-8?years old were evaluated before (T0), 1?month (T1), and 6?months (T2) after intestinal mobilization, recording Bristol stool scale scores, urinary p-cresol concentrations, and behavioral scores for social interaction deficits, stereotypic behaviors, anxiety, and hyperactivity. Gut mobilization yielded a progressive and highly significant decrease in all behavioral symptoms over the 6-month study period. Urinary p-cresol levels displayed variable trends not significantly correlated with changes in behavioral parameters, mainly increasing at T1 and decreasing at T2. These results support gut mobilization as a simple strategy to ameliorate ASD symptoms, as well as comorbid anxiety and hyperactivity, in chronically constipated children. Variation in p-cresol absorption seemingly provides limited contributions, if any, to these behavioral changes. Further research will be needed to address the relative role of reduced abdominal discomfort following mobilization, as compared to specific modifications in microbiome composition and in gut bacteria-derived neuroactive compounds. En ligne : http://dx.doi.org/10.1002/aur.2639 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=450

Preference for biological motion is reduced in ASD: implications for clinical trials and the search for biomarkers / L. MASON in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 74 p. Titre : Preference for biological motion is reduced in ASD: implications for clinical trials and the search for biomarkers Type de document : Texte imprimé et/ou numérique Auteurs : L. MASON, Auteur ; F. SHIC, Auteur ; T. FALCK-YTTER, Auteur ; Bhismadev CHAKRABARTI, Auteur ; Tony CHARMAN, Auteur ; E. LOTH, Auteur ; J. TILLMANN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sven BÖLTE, Auteur ; Jan K. BUITELAAR, Auteur ; S. DURSTON, Auteur ; B. ORANJE, Auteur ; A. M. PERSICO, Auteur ; C. BECKMANN, Auteur ; T. BOUGERON, Auteur ; F. DELL'ACQUA, Auteur ; C. ECKER, Auteur ; C. MOESSNANG, Auteur ; D. MURPHY, Auteur ; M. H. JOHNSON, Auteur ; E. J. H. JONES, Auteur Article en page(s) : 74 p. Langues : Anglais (eng) Mots-clés : Autism  Biological motion  Biomarker  Development  Eye tracking  in the last 3 years acted as an author, consultant or lecturer for Medice and Roche.  He receives royalties for text books and diagnostic tools from Hogrefe, Kohlhammer  and UTB. JB has been in the past 3 years a consultant to/member of advisory board  of/and/or speaker for Takeda/Shire, Roche, Medice, Angelini, Janssen and Servier. He  is not an employee of any of these companies and not a stock shareholder of any of  these companies. He has no other financial or material support, including expert  testimony, patents, royalties. Index. décimale : PER Périodiques Résumé : BACKGROUND: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology. METHODS: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N?=?282) and non-autistic control (N?=?204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL). RESULTS: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline. LIMITATIONS: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons. CONCLUSIONS: Biological motion preference elicits small-to-medium-sized case-control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear. En ligne : http://dx.doi.org/10.1186/s13229-021-00476-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Preference for biological motion is reduced in ASD: implications for clinical trials and the search for biomarkers [Texte imprimé et/ou numérique] / L. MASON, Auteur ; F. SHIC, Auteur ; T. FALCK-YTTER, Auteur ; Bhismadev CHAKRABARTI, Auteur ; Tony CHARMAN, Auteur ; E. LOTH, Auteur ; J. TILLMANN, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sven BÖLTE, Auteur ; Jan K. BUITELAAR, Auteur ; S. DURSTON, Auteur ; B. ORANJE, Auteur ; A. M. PERSICO, Auteur ; C. BECKMANN, Auteur ; T. BOUGERON, Auteur ; F. DELL'ACQUA, Auteur ; C. ECKER, Auteur ; C. MOESSNANG, Auteur ; D. MURPHY, Auteur ; M. H. JOHNSON, Auteur ; E. J. H. JONES, Auteur . - 74 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 74 p. Mots-clés : Autism  Biological motion  Biomarker  Development  Eye tracking  in the last 3 years acted as an author, consultant or lecturer for Medice and Roche.  He receives royalties for text books and diagnostic tools from Hogrefe, Kohlhammer  and UTB. JB has been in the past 3 years a consultant to/member of advisory board  of/and/or speaker for Takeda/Shire, Roche, Medice, Angelini, Janssen and Servier. He  is not an employee of any of these companies and not a stock shareholder of any of  these companies. He has no other financial or material support, including expert  testimony, patents, royalties. Index. décimale : PER Périodiques Résumé : BACKGROUND: The neurocognitive mechanisms underlying autism spectrum disorder (ASD) remain unclear. Progress has been largely hampered by small sample sizes, variable age ranges and resulting inconsistent findings. There is a pressing need for large definitive studies to delineate the nature and extent of key case/control differences to direct research towards fruitful areas for future investigation. Here we focus on perception of biological motion, a promising index of social brain function which may be altered in ASD. In a large sample ranging from childhood to adulthood, we assess whether biological motion preference differs in ASD compared to neurotypical participants (NT), how differences are modulated by age and sex and whether they are associated with dimensional variation in concurrent or later symptomatology. METHODS: Eye-tracking data were collected from 486 6-to-30-year-old autistic (N?=?282) and non-autistic control (N?=?204) participants whilst they viewed 28 trials pairing biological (BM) and control (non-biological, CTRL) motion. Preference for the biological motion stimulus was calculated as (1) proportion looking time difference (BM-CTRL) and (2) peak look duration difference (BM-CTRL). RESULTS: The ASD group showed a present but weaker preference for biological motion than the NT group. The nature of the control stimulus modulated preference for biological motion in both groups. Biological motion preference did not vary with age, gender, or concurrent or prospective social communicative skill within the ASD group, although a lack of clear preference for either stimulus was associated with higher social-communicative symptoms at baseline. LIMITATIONS: The paired visual preference we used may underestimate preference for a stimulus in younger and lower IQ individuals. Our ASD group had a lower average IQ by approximately seven points. 18% of our sample was not analysed for various technical and behavioural reasons. CONCLUSIONS: Biological motion preference elicits small-to-medium-sized case-control effects, but individual differences do not strongly relate to core social autism associated symptomatology. We interpret this as an autistic difference (as opposed to a deficit) likely manifest in social brain regions. The extent to which this is an innate difference present from birth and central to the autistic phenotype, or the consequence of a life lived with ASD, is unclear. En ligne : http://dx.doi.org/10.1186/s13229-021-00476-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

The EU-AIMS Longitudinal European Autism Project (LEAP): clinical characterisation / Tony CHARMAN in Molecular Autism, 8 (2017)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 27p. Titre : The EU-AIMS Longitudinal European Autism Project (LEAP): clinical characterisation Type de document : Texte imprimé et/ou numérique Auteurs : Tony CHARMAN, Auteur ; E. LOTH, Auteur ; J. TILLMANN, Auteur ; D. CRAWLEY, Auteur ; C. WOOLDRIDGE, Auteur ; D. GOYARD, Auteur ; Jumana AHMAD, Auteur ; Bonnie AUYEUNG, Auteur ; S. AMBROSINO, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sarah BAUMEISTER, Auteur ; C. BECKMANN, Auteur ; Sven BÖLTE, Auteur ; Thomas BOURGERON, Auteur ; Carsten BOURS, Auteur ; Michael BRAMMER, Auteur ; Daniel BRANDEIS, Auteur ; C. BROGNA, Auteur ; Y. DE BRUIJN, Auteur ; Bhismadev CHAKRABARTI, Auteur ; I. CORNELISSEN, Auteur ; F. D. ACQUA, Auteur ; G. DUMAS, Auteur ; S. DURSTON, Auteur ; C. ECKER, Auteur ; J. FAULKNER, Auteur ; V. FROUIN, Auteur ; P. GARCES, Auteur ; L. HAM, Auteur ; H. HAYWARD, Auteur ; J. HIPP, Auteur ; R. J. HOLT, Auteur ; J. ISAKSSON, Auteur ; M. H. JOHNSON, Auteur ; E. J. H. JONES, Auteur ; P. KUNDU, Auteur ; Meng-Chuan LAI, Auteur ; L. D'ARDHUY X, Auteur ; M. V. LOMBARDO, Auteur ; D. J. LYTHGOE, Auteur ; R. MANDL, Auteur ; L. MASON, Auteur ; A. MEYER-LINDENBERG, Auteur ; C. MOESSNANG, Auteur ; N. MUELLER, Auteur ; L. O'DWYER, Auteur ; M. OLDEHINKEL, Auteur ; B. ORANJE, Auteur ; Gahan PANDINA, Auteur ; A. M. PERSICO, Auteur ; B. RUGGERI, Auteur ; A. N. V. RUIGROK, Auteur ; J. SABET, Auteur ; R. SACCO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; E. SIMONOFF, Auteur ; R. TORO, Auteur ; H. TOST, Auteur ; J. WALDMAN, Auteur ; S. C. R. WILLIAMS, Auteur ; M. P. ZWIERS, Auteur ; W. SPOOREN, Auteur ; D. G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur Article en page(s) : 27p. Langues : Anglais (eng) Mots-clés : Age  Autism  Autism spectrum disorder  Behaviours  Heterogeneity  Iq  Phenotype  Sex Index. décimale : PER Périodiques Résumé : BACKGROUND: The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study on biomarkers for autism spectrum disorder (ASD). The current paper describes the clinical characteristics of the LEAP cohort and examines age, sex and IQ differences in ASD core symptoms and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers. METHODS: From six research centres in four European countries, we recruited 437 children and adults with ASD and 300 controls between the ages of 6 and 30 years with IQs varying between 50 and 148. We conducted in-depth clinical characterisation including a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms. RESULTS: The cohort showed heterogeneity in ASD symptom presentation, with only minimal to moderate site differences on core clinical and cognitive measures. On both parent-report interview and questionnaire measures, ASD symptom severity was lower in adults compared to children and adolescents. The precise pattern of differences varied across measures, but there was some evidence of both lower social symptoms and lower repetitive behaviour severity in adults. Males had higher ASD symptom scores than females on clinician-rated and parent interview diagnostic measures but not on parent-reported dimensional measures of ASD symptoms. In contrast, self-reported ASD symptom severity was higher in adults compared to adolescents, and in adult females compared to males. Higher scores on ASD symptom measures were moderately associated with lower IQ. Both inattentive and hyperactive/impulsive ADHD symptoms were lower in adults than in children and adolescents, and males with ASD had higher levels of inattentive and hyperactive/impulsive ADHD symptoms than females. CONCLUSIONS: The established phenotypic heterogeneity in ASD is well captured in the LEAP cohort. Variation both in core ASD symptom severity and in commonly co-occurring psychiatric symptoms were systematically associated with sex, age and IQ. The pattern of ASD symptom differences with age and sex also varied by whether these were clinician ratings or parent- or self-reported which has important implications for establishing stratification biomarkers and for their potential use as outcome measures in clinical trials. En ligne : http://dx.doi.org/10.1186/s13229-017-0145-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329 [article] The EU-AIMS Longitudinal European Autism Project (LEAP): clinical characterisation [Texte imprimé et/ou numérique] / Tony CHARMAN, Auteur ; E. LOTH, Auteur ; J. TILLMANN, Auteur ; D. CRAWLEY, Auteur ; C. WOOLDRIDGE, Auteur ; D. GOYARD, Auteur ; Jumana AHMAD, Auteur ; Bonnie AUYEUNG, Auteur ; S. AMBROSINO, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sarah BAUMEISTER, Auteur ; C. BECKMANN, Auteur ; Sven BÖLTE, Auteur ; Thomas BOURGERON, Auteur ; Carsten BOURS, Auteur ; Michael BRAMMER, Auteur ; Daniel BRANDEIS, Auteur ; C. BROGNA, Auteur ; Y. DE BRUIJN, Auteur ; Bhismadev CHAKRABARTI, Auteur ; I. CORNELISSEN, Auteur ; F. D. ACQUA, Auteur ; G. DUMAS, Auteur ; S. DURSTON, Auteur ; C. ECKER, Auteur ; J. FAULKNER, Auteur ; V. FROUIN, Auteur ; P. GARCES, Auteur ; L. HAM, Auteur ; H. HAYWARD, Auteur ; J. HIPP, Auteur ; R. J. HOLT, Auteur ; J. ISAKSSON, Auteur ; M. H. JOHNSON, Auteur ; E. J. H. JONES, Auteur ; P. KUNDU, Auteur ; Meng-Chuan LAI, Auteur ; L. D'ARDHUY X, Auteur ; M. V. LOMBARDO, Auteur ; D. J. LYTHGOE, Auteur ; R. MANDL, Auteur ; L. MASON, Auteur ; A. MEYER-LINDENBERG, Auteur ; C. MOESSNANG, Auteur ; N. MUELLER, Auteur ; L. O'DWYER, Auteur ; M. OLDEHINKEL, Auteur ; B. ORANJE, Auteur ; Gahan PANDINA, Auteur ; A. M. PERSICO, Auteur ; B. RUGGERI, Auteur ; A. N. V. RUIGROK, Auteur ; J. SABET, Auteur ; R. SACCO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; E. SIMONOFF, Auteur ; R. TORO, Auteur ; H. TOST, Auteur ; J. WALDMAN, Auteur ; S. C. R. WILLIAMS, Auteur ; M. P. ZWIERS, Auteur ; W. SPOOREN, Auteur ; D. G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur . - 27p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 27p. Mots-clés : Age  Autism  Autism spectrum disorder  Behaviours  Heterogeneity  Iq  Phenotype  Sex Index. décimale : PER Périodiques Résumé : BACKGROUND: The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study on biomarkers for autism spectrum disorder (ASD). The current paper describes the clinical characteristics of the LEAP cohort and examines age, sex and IQ differences in ASD core symptoms and common co-occurring psychiatric symptoms. A companion paper describes the overall design and experimental protocol and outlines the strategy to identify stratification biomarkers. METHODS: From six research centres in four European countries, we recruited 437 children and adults with ASD and 300 controls between the ages of 6 and 30 years with IQs varying between 50 and 148. We conducted in-depth clinical characterisation including a wide range of observational, interview and questionnaire measures of the ASD phenotype, as well as co-occurring psychiatric symptoms. RESULTS: The cohort showed heterogeneity in ASD symptom presentation, with only minimal to moderate site differences on core clinical and cognitive measures. On both parent-report interview and questionnaire measures, ASD symptom severity was lower in adults compared to children and adolescents. The precise pattern of differences varied across measures, but there was some evidence of both lower social symptoms and lower repetitive behaviour severity in adults. Males had higher ASD symptom scores than females on clinician-rated and parent interview diagnostic measures but not on parent-reported dimensional measures of ASD symptoms. In contrast, self-reported ASD symptom severity was higher in adults compared to adolescents, and in adult females compared to males. Higher scores on ASD symptom measures were moderately associated with lower IQ. Both inattentive and hyperactive/impulsive ADHD symptoms were lower in adults than in children and adolescents, and males with ASD had higher levels of inattentive and hyperactive/impulsive ADHD symptoms than females. CONCLUSIONS: The established phenotypic heterogeneity in ASD is well captured in the LEAP cohort. Variation both in core ASD symptom severity and in commonly co-occurring psychiatric symptoms were systematically associated with sex, age and IQ. The pattern of ASD symptom differences with age and sex also varied by whether these were clinician ratings or parent- or self-reported which has important implications for establishing stratification biomarkers and for their potential use as outcome measures in clinical trials. En ligne : http://dx.doi.org/10.1186/s13229-017-0145-9 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=329

The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders / E. LOTH in Molecular Autism, 8 (2017)  

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Urinary metabolomics of young Italian autistic children supports abnormal tryptophan and purine metabolism / F. GEVI in Molecular Autism, 7 (2016)  

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