Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine / R. H. WICHERS in Molecular Autism, 12 (2021)  

Public ISBD [article]  inMolecular Autism > 12 (2021) . - 14 p. Titre : Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine Type de document : Texte imprimé et/ou numérique Auteurs : R. H. WICHERS, Auteur ; J. L. FINDON, Auteur ; A. JELSMA, Auteur ; V. GIAMPIETRO, Auteur ; V. STOENCHEVA, Auteur ; D. M. ROBERTSON, Auteur ; C. M. MURPHY, Auteur ; S. BLAINEY, Auteur ; G. MCALONAN, Auteur ; C. ECKER, Auteur ; K. RUBIA, Auteur ; D. G. M. MURPHY, Auteur ; Eileen DALY, Auteur Article en page(s) : 14 p. Langues : Anglais (eng) Mots-clés : Adult  Antidepressive Agents, Tricyclic/therapeutic use  Attention/drug effects  Autistic Disorder/diagnostic imaging/drug therapy/physiopathology/psychology  Brain/diagnostic imaging/physiopathology  Cross-Over Studies  Double-Blind Method  Executive Function/drug effects  Humans  Magnetic Resonance Imaging  Male  Middle Aged  Pilot Projects  Thiazepines/therapeutic use  Young Adult  Autism spectrum disorder  Executive functioning  Serotonin  Tianeptine  fMRI  grants from Lilly and Shire. The other authors declare that they have no competing  interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occurring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved both in regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. METHOD: We conducted a pharmacological magnetic resonance imaging study, using a randomized double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during two EF tasks (of response inhibition and sustained attention) in 38 adult males: 19 with ASD and 19 matched controls. RESULTS: Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibition regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case-control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices. LIMITATIONS: We conducted a pilot study using a single dose of tianeptine, and therefore, we cannot comment on long-term outcome. CONCLUSIONS: Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine and whether it improves clinical symptoms. En ligne : http://dx.doi.org/10.1186/s13229-021-00422-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 [article] Modulation of atypical brain activation during executive functioning in autism: a pharmacological MRI study of tianeptine [Texte imprimé et/ou numérique] / R. H. WICHERS, Auteur ; J. L. FINDON, Auteur ; A. JELSMA, Auteur ; V. GIAMPIETRO, Auteur ; V. STOENCHEVA, Auteur ; D. M. ROBERTSON, Auteur ; C. M. MURPHY, Auteur ; S. BLAINEY, Auteur ; G. MCALONAN, Auteur ; C. ECKER, Auteur ; K. RUBIA, Auteur ; D. G. M. MURPHY, Auteur ; Eileen DALY, Auteur . - 14 p. Langues : Anglais (eng) in Molecular Autism > 12 (2021) . - 14 p. Mots-clés : Adult  Antidepressive Agents, Tricyclic/therapeutic use  Attention/drug effects  Autistic Disorder/diagnostic imaging/drug therapy/physiopathology/psychology  Brain/diagnostic imaging/physiopathology  Cross-Over Studies  Double-Blind Method  Executive Function/drug effects  Humans  Magnetic Resonance Imaging  Male  Middle Aged  Pilot Projects  Thiazepines/therapeutic use  Young Adult  Autism spectrum disorder  Executive functioning  Serotonin  Tianeptine  fMRI  grants from Lilly and Shire. The other authors declare that they have no competing  interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is associated with deficits in executive functioning (EF), and these have been suggested to contribute to core as well as co-occurring psychiatric symptoms. The biological basis of these deficits is unknown but may include the serotonergic system, which is involved both in regulating EF in neurotypical populations and in the pathophysiology of ASD. We previously demonstrated that reducing serotonin by acute tryptophan depletion (ATD) shifts differences in brain function during performance of EF tasks towards control levels. However, ATD cannot be easily used in the clinic, and we therefore need to adopt alternative approaches to challenge the serotonin system. Hence, we investigated the role of the serotonergic modulator tianeptine on EF networks in ASD. METHOD: We conducted a pharmacological magnetic resonance imaging study, using a randomized double-blind crossover design, to compare the effect of an acute dosage of 12.5 mg tianeptine and placebo on brain activation during two EF tasks (of response inhibition and sustained attention) in 38 adult males: 19 with ASD and 19 matched controls. RESULTS: Under placebo, compared to controls, individuals with ASD had atypical brain activation in response inhibition regions including the inferior frontal cortex, premotor regions and cerebellum. During sustained attention, individuals with ASD had decreased brain activation in the right middle temporal cortex, right cuneus and left precuneus. Most of the case-control differences in brain function observed under placebo conditions were abolished by tianeptine administration. Also, within ASD individuals, brain functional differences were shifted significantly towards control levels during response inhibition in the inferior frontal and premotor cortices. LIMITATIONS: We conducted a pilot study using a single dose of tianeptine, and therefore, we cannot comment on long-term outcome. CONCLUSIONS: Our findings provide the first evidence that tianeptine can shift atypical brain activation during EF in adults with ASD towards control levels. Future studies should investigate whether this shift in the biology of ASD is maintained after prolonged treatment with tianeptine and whether it improves clinical symptoms. En ligne : http://dx.doi.org/10.1186/s13229-021-00422-0 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459

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 effect of age on vertex-based measures of the grey-white matter tissue contrast in autism spectrum disorder / C. MANN in Molecular Autism, 9 (2018)  

Public ISBD [article]  inMolecular Autism > 9 (2018) . - 49p. Titre : The effect of age on vertex-based measures of the grey-white matter tissue contrast in autism spectrum disorder Type de document : Texte imprimé et/ou numérique Auteurs : C. MANN, Auteur ; Anke BLETSCH, Auteur ; D. ANDREWS, Auteur ; Eileen DALY, Auteur ; C. MURPHY, Auteur ; D. MURPHY, Auteur ; C. ECKER, Auteur Article en page(s) : 49p. Langues : Anglais (eng) Mots-clés : Autism spectrum disorder  Brain anatomy  Neurodevelopment  Neuroimaging  Structural MRI  Psychosomatics and Psychotherapy, University Hospital, Goethe-University  Frankfurt am Main, Deutschordenstrasse 50, 60528 Frankfurt, Germany  DA, PhD, The  Medical Investigation of Neurodevelopmental Disorders (MIND) Institute and  Department of Psychiatry and Behavioural Sciences, UC Davis School of Medicine,  University of California Davis, Sacramento, CA, USA  ED, PhD and CM, PhD,  Department of Forensic and Neurodevelopmental Sciences, and the Sackler Institute  for Translational Neurodevelopmental Sciences, Institute of Psychiatry,  Psychology & Neuroscience (IoPPN), King's College London, London SE5 8AF, United  Kingdom  DM, Professor, Head of Department of Forensic and Neurodevelopmental  Sciences, and the Sackler Institute for Translational Neurodevelopmental  Sciences, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's  College London, London SE5 8AF, United Kingdom  CE, Professor, Department of  Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University  Hospital, Goethe-University Frankfurt am Main, Deutschordenstrasse 50, 60528  Frankfurt, Germany and Department of Forensic and Neurodevelopmental Sciences,  and the Sackler Institute for Translational Neurodevelopmental Sciences,  Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College  London, London SE5 8AF, United Kingdom.All participants gave informed written  consent in accordance with the ethics approval by the National Research Ethics  Committee, Suffolk, England.Not applicable.The authors declare that they have no  competing interests.Springer Nature remains neutral with regard to jurisdictional  claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Histological evidence suggests that autism spectrum disorder (ASD) is accompanied by a reduced integrity of the grey-white matter boundary. This has also recently been confirmed by a structural neuroimaging study in vivo reporting significantly reduced grey-white matter tissue contrast (GWC) in adult individuals (18-42 years of age) with ASD relative to typically developing (TD) controls. However, it remains unknown whether the neuroanatomical differences in ASD at the grey-white matter boundary are stable across development or are age-dependent. Methods: Here, we examined differences in the neurodevelopmental trajectories of GWC in a cross-sectional sample of 77 male ASD individuals and 76 typically developing (TD) controls across childhood and early adulthood (from 7 to 25 years). Results: Using nested model comparisons, we first established that the developmental trajectory of GWC is complex in many regions across the cortex and includes linear and non-linear effects of age. Second, while ASD individuals have significantly reduced GWC overall, these differences are age-dependent and are most prominent during childhood (< 15 years). Conclusions: Taken together, our findings suggest that differences in GWC in ASD are unlikely to reflect atypical grey matter cytoarchitecture alone, but may also represent other aspects of the cortical architecture such as age-dependent variability in myelin integrity. En ligne : https://dx.doi.org/10.1186/s13229-018-0232-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371 [article] The effect of age on vertex-based measures of the grey-white matter tissue contrast in autism spectrum disorder [Texte imprimé et/ou numérique] / C. MANN, Auteur ; Anke BLETSCH, Auteur ; D. ANDREWS, Auteur ; Eileen DALY, Auteur ; C. MURPHY, Auteur ; D. MURPHY, Auteur ; C. ECKER, Auteur . - 49p. Langues : Anglais (eng) in Molecular Autism > 9 (2018) . - 49p. Mots-clés : Autism spectrum disorder  Brain anatomy  Neurodevelopment  Neuroimaging  Structural MRI  Psychosomatics and Psychotherapy, University Hospital, Goethe-University  Frankfurt am Main, Deutschordenstrasse 50, 60528 Frankfurt, Germany  DA, PhD, The  Medical Investigation of Neurodevelopmental Disorders (MIND) Institute and  Department of Psychiatry and Behavioural Sciences, UC Davis School of Medicine,  University of California Davis, Sacramento, CA, USA  ED, PhD and CM, PhD,  Department of Forensic and Neurodevelopmental Sciences, and the Sackler Institute  for Translational Neurodevelopmental Sciences, Institute of Psychiatry,  Psychology & Neuroscience (IoPPN), King's College London, London SE5 8AF, United  Kingdom  DM, Professor, Head of Department of Forensic and Neurodevelopmental  Sciences, and the Sackler Institute for Translational Neurodevelopmental  Sciences, Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's  College London, London SE5 8AF, United Kingdom  CE, Professor, Department of  Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University  Hospital, Goethe-University Frankfurt am Main, Deutschordenstrasse 50, 60528  Frankfurt, Germany and Department of Forensic and Neurodevelopmental Sciences,  and the Sackler Institute for Translational Neurodevelopmental Sciences,  Institute of Psychiatry, Psychology & Neuroscience (IoPPN), King's College  London, London SE5 8AF, United Kingdom.All participants gave informed written  consent in accordance with the ethics approval by the National Research Ethics  Committee, Suffolk, England.Not applicable.The authors declare that they have no  competing interests.Springer Nature remains neutral with regard to jurisdictional  claims in published maps and institutional affiliations. Index. décimale : PER Périodiques Résumé : Background: Histological evidence suggests that autism spectrum disorder (ASD) is accompanied by a reduced integrity of the grey-white matter boundary. This has also recently been confirmed by a structural neuroimaging study in vivo reporting significantly reduced grey-white matter tissue contrast (GWC) in adult individuals (18-42 years of age) with ASD relative to typically developing (TD) controls. However, it remains unknown whether the neuroanatomical differences in ASD at the grey-white matter boundary are stable across development or are age-dependent. Methods: Here, we examined differences in the neurodevelopmental trajectories of GWC in a cross-sectional sample of 77 male ASD individuals and 76 typically developing (TD) controls across childhood and early adulthood (from 7 to 25 years). Results: Using nested model comparisons, we first established that the developmental trajectory of GWC is complex in many regions across the cortex and includes linear and non-linear effects of age. Second, while ASD individuals have significantly reduced GWC overall, these differences are age-dependent and are most prominent during childhood (< 15 years). Conclusions: Taken together, our findings suggest that differences in GWC in ASD are unlikely to reflect atypical grey matter cytoarchitecture alone, but may also represent other aspects of the cortical architecture such as age-dependent variability in myelin integrity. En ligne : https://dx.doi.org/10.1186/s13229-018-0232-6 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=371

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)  

Public ISBD [article]  inMolecular Autism > 8 (2017) . - 24p. Titre : The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders Type de document : Texte imprimé et/ou numérique Auteurs : E. LOTH, Auteur ; Tony CHARMAN, Auteur ; L. MASON, Auteur ; J. TILLMANN, Auteur ; E. J. H. JONES, Auteur ; C. WOOLDRIDGE, Auteur ; Jumana AHMAD, Auteur ; Bonnie AUYEUNG, Auteur ; C. BROGNA, Auteur ; S. AMBROSINO, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sarah BAUMEISTER, Auteur ; C. BECKMANN, Auteur ; Michael BRAMMER, Auteur ; Daniel BRANDEIS, Auteur ; Sven BÖLTE, Auteur ; Thomas BOURGERON, Auteur ; Carsten BOURS, Auteur ; Y. DE BRUIJN, Auteur ; Bhismadev CHAKRABARTI, Auteur ; D. CRAWLEY, 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 ; D. GOYARD, Auteur ; H. HAYWARD, Auteur ; L. M. HAM, Auteur ; J. HIPP, Auteur ; R. J. HOLT, Auteur ; M. H. JOHNSON, Auteur ; J. ISAKSSON, Auteur ; P. KUNDU, Auteur ; Meng-Chuan LAI, Auteur ; L. D'ARDHUY X, Auteur ; M. V. LOMBARDO, Auteur ; D. J. LYTHGOE, Auteur ; R. MANDL, 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 ; A. N. V. RUIGROK, Auteur ; B. RUGGERI, 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) : 24p. Langues : Anglais (eng) Mots-clés : Biomarkers  Cognition  Eeg  Eye-tracking  Genetics  Mri  Neuroimaging Index. décimale : PER Périodiques Résumé : BACKGROUND: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. METHODS: LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. RESULTS: Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). CONCLUSION: We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. En ligne : http://dx.doi.org/10.1186/s13229-017-0146-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330 [article] The EU-AIMS Longitudinal European Autism Project (LEAP): design and methodologies to identify and validate stratification biomarkers for autism spectrum disorders [Texte imprimé et/ou numérique] / E. LOTH, Auteur ; Tony CHARMAN, Auteur ; L. MASON, Auteur ; J. TILLMANN, Auteur ; E. J. H. JONES, Auteur ; C. WOOLDRIDGE, Auteur ; Jumana AHMAD, Auteur ; Bonnie AUYEUNG, Auteur ; C. BROGNA, Auteur ; S. AMBROSINO, Auteur ; Tobias BANASCHEWSKI, Auteur ; Simon BARON-COHEN, Auteur ; Sarah BAUMEISTER, Auteur ; C. BECKMANN, Auteur ; Michael BRAMMER, Auteur ; Daniel BRANDEIS, Auteur ; Sven BÖLTE, Auteur ; Thomas BOURGERON, Auteur ; Carsten BOURS, Auteur ; Y. DE BRUIJN, Auteur ; Bhismadev CHAKRABARTI, Auteur ; D. CRAWLEY, 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 ; D. GOYARD, Auteur ; H. HAYWARD, Auteur ; L. M. HAM, Auteur ; J. HIPP, Auteur ; R. J. HOLT, Auteur ; M. H. JOHNSON, Auteur ; J. ISAKSSON, Auteur ; P. KUNDU, Auteur ; Meng-Chuan LAI, Auteur ; L. D'ARDHUY X, Auteur ; M. V. LOMBARDO, Auteur ; D. J. LYTHGOE, Auteur ; R. MANDL, 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 ; A. N. V. RUIGROK, Auteur ; B. RUGGERI, 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 . - 24p. Langues : Anglais (eng) in Molecular Autism > 8 (2017) . - 24p. Mots-clés : Biomarkers  Cognition  Eeg  Eye-tracking  Genetics  Mri  Neuroimaging Index. décimale : PER Périodiques Résumé : BACKGROUND: The tremendous clinical and aetiological diversity among individuals with autism spectrum disorder (ASD) has been a major obstacle to the development of new treatments, as many may only be effective in particular subgroups. Precision medicine approaches aim to overcome this challenge by combining pathophysiologically based treatments with stratification biomarkers that predict which treatment may be most beneficial for particular individuals. However, so far, we have no single validated stratification biomarker for ASD. This may be due to the fact that most research studies primarily have focused on the identification of mean case-control differences, rather than within-group variability, and included small samples that were underpowered for stratification approaches. The EU-AIMS Longitudinal European Autism Project (LEAP) is to date the largest multi-centre, multi-disciplinary observational study worldwide that aims to identify and validate stratification biomarkers for ASD. METHODS: LEAP includes 437 children and adults with ASD and 300 individuals with typical development or mild intellectual disability. Using an accelerated longitudinal design, each participant is comprehensively characterised in terms of clinical symptoms, comorbidities, functional outcomes, neurocognitive profile, brain structure and function, biochemical markers and genomics. In addition, 51 twin-pairs (of which 36 had one sibling with ASD) are included to identify genetic and environmental factors in phenotypic variability. RESULTS: Here, we describe the demographic characteristics of the cohort, planned analytic stratification approaches, criteria and steps to validate candidate stratification markers, pre-registration procedures to increase transparency, standardisation and data robustness across all analyses, and share some 'lessons learnt'. A clinical characterisation of the cohort is given in the companion paper (Charman et al., accepted). CONCLUSION: We expect that LEAP will enable us to confirm, reject and refine current hypotheses of neurocognitive/neurobiological abnormalities, identify biologically and clinically meaningful ASD subgroups, and help us map phenotypic heterogeneity to different aetiologies. En ligne : http://dx.doi.org/10.1186/s13229-017-0146-8 Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=330

Towards robust and replicable sex differences in the intrinsic brain function of autism / D. L. FLORIS in Molecular Autism, 12 (2021)  

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