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Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys / O. OZTAN in Molecular Autism, 12 (2021)
[article]
Titre : Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys Type de document : Texte imprimé et/ou numérique Auteurs : O. OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; E. ARGILLI, Auteur ; A. C. MANESS, Auteur ; S. M. SIMMONS, Auteur ; N. MOHSIN, Auteur ; L. A. DEL ROSSO, Auteur ; J. P. GARNER, Auteur ; E. H. SHERR, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur Article en page(s) : 50 p. Langues : Anglais (eng) Mots-clés : Arginine vasopressin Autism spectrum disorder Biomarker Cerebrospinal fluid Kinase signaling pathway Oxytocin Rhesus macaque Social responsiveness scale Social trait variation the University of California, San Francisco (UCSF) have filed patent applications related to biological measures studied herein (Stanford University: PCT/US2019/019029 “Methods for diagnosing and for determining severity of an autism spectrum disorder” UCSF: PCT/US2016/014623 “Methods of diagnosing and treating autism spectrum disorders”). These patents have not been granted or licensed, and no study author is receiving any financial compensation at this time. EHS serves on the advisory board for Retrophin Inc. All other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1-3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores. METHODS: Cerebrospinal fluid and blood samples were collected from N?=?76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n?=?43), samples were collected thrice over a 10-month period. The following statistical tests were used: "Case 2A" intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling. RESULTS: All biological measures (except AKT) showed significant test-retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n?=?57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n?=?75 of the subjects). CONCLUSIONS: These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys. En ligne : http://dx.doi.org/10.1186/s13229-021-00442-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 12 (2021) . - 50 p.[article] Autism-associated biomarkers: test-retest reliability and relationship to quantitative social trait variation in rhesus monkeys [Texte imprimé et/ou numérique] / O. OZTAN, Auteur ; Catherine F. TALBOT, Auteur ; E. ARGILLI, Auteur ; A. C. MANESS, Auteur ; S. M. SIMMONS, Auteur ; N. MOHSIN, Auteur ; L. A. DEL ROSSO, Auteur ; J. P. GARNER, Auteur ; E. H. SHERR, Auteur ; John P. CAPITANIO, Auteur ; Karen J. PARKER, Auteur . - 50 p.
Langues : Anglais (eng)
in Molecular Autism > 12 (2021) . - 50 p.
Mots-clés : Arginine vasopressin Autism spectrum disorder Biomarker Cerebrospinal fluid Kinase signaling pathway Oxytocin Rhesus macaque Social responsiveness scale Social trait variation the University of California, San Francisco (UCSF) have filed patent applications related to biological measures studied herein (Stanford University: PCT/US2019/019029 “Methods for diagnosing and for determining severity of an autism spectrum disorder” UCSF: PCT/US2016/014623 “Methods of diagnosing and treating autism spectrum disorders”). These patents have not been granted or licensed, and no study author is receiving any financial compensation at this time. EHS serves on the advisory board for Retrophin Inc. All other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Rhesus monkeys (Macaca mulatta) exhibit pronounced individual differences in social traits as measured by the macaque Social Responsiveness Scale-Revised. The macaque Social Responsiveness Scale was previously adapted from the Social Responsiveness Scale, an instrument designed to assess social and autistic trait variation in humans. To better understand potential biological underpinnings of this behavioral variation, we evaluated the trait-like consistency of several biological measures previously implicated in autism (e.g., arginine vasopressin, oxytocin, and their receptors, as well as ERK1/2, PTEN, and AKT(1-3) from the RAS-MAPK and PI3K-AKT pathways). We also tested which biological measures predicted macaque Social Responsiveness Scale-Revised scores. METHODS: Cerebrospinal fluid and blood samples were collected from N?=?76 male monkeys, which, as a sample, showed a continuous distribution on the macaque Social Responsiveness Scale-Revised. In a subset of these subjects (n?=?43), samples were collected thrice over a 10-month period. The following statistical tests were used: "Case 2A" intra-class correlation coefficients of consistency, principal component analysis, and general linear modeling. RESULTS: All biological measures (except AKT) showed significant test-retest reliability within individuals across time points. We next performed principal component analysis on data from monkeys with complete biological measurement sets at the first time point (n?=?57), to explore potential correlations between the reliable biological measures and their relationship to macaque Social Responsiveness Scale-Revised score; a three-component solution was found. Follow-up analyses revealed that cerebrospinal fluid arginine vasopressin concentration, but no other biological measure, robustly predicted individual differences in macaque Social Responsiveness Scale-Revised scores, such that monkeys with the lowest cerebrospinal fluid arginine vasopressin concentration exhibited the greatest social impairment. Finally, we confirmed that this result held in the larger study sample (in which cerebrospinal fluid arginine vasopressin values were available from n?=?75 of the subjects). CONCLUSIONS: These findings indicate that cerebrospinal fluid arginine vasopressin concentration is a stable trait-like measure and that it is linked to quantitative social trait variation in male rhesus monkeys. En ligne : http://dx.doi.org/10.1186/s13229-021-00442-w Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459 Social brain activation during mentalizing in a large autism cohort: the Longitudinal European Autism Project / Carolin MOESSNANG in Molecular Autism, 11 (2020)
[article]
Titre : Social brain activation during mentalizing in a large autism cohort: the Longitudinal European Autism Project Type de document : Texte imprimé et/ou numérique Auteurs : Carolin MOESSNANG, Auteur ; Sarah BAUMEISTER, Auteur ; Julian TILLMANN, Auteur ; David GOYARD, Auteur ; Tony CHARMAN, Auteur ; Sara AMBROSINO, Auteur ; Simon BARON-COHEN, Auteur ; Christian F. BECKMANN, Auteur ; Sven BÖLTE, Auteur ; Carsten BOURS, Auteur ; Daisy CRAWLEY, Auteur ; Flavio DELL'ACQUA, Auteur ; Sarah DURSTON, Auteur ; Christine ECKER, Auteur ; Vincent FROUIN, Auteur ; Hannah HAYWARD, Auteur ; Rosemary HOLT, Auteur ; Mark H. JOHNSON, Auteur ; Emily JONES, Auteur ; Meng-Chuan LAI, Auteur ; Michael V. LOMBARDO, Auteur ; Luke MASON, Auteur ; Marianne OLDENHINKEL, Auteur ; Antonio PERSICO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; Will SPOOREN, Auteur ; Eva LOTH, Auteur ; Declan G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Tobias BANASCHEWSKI, Auteur ; Daniel BRANDEIS, Auteur ; Heike TOST, Auteur ; Andreas MEYER-LINDENBERG, Auteur Article en page(s) : 17 p. Langues : Anglais (eng) Mots-clés : Animated shapes Autism Autism spectrum disorder Development Mentalizing Multi-site Social brain Theory of mind fMRI Science, Atheneum Partners, Blueprint Partnership, Boehringer Ingelheim, Daimler und Benz Stiftung, Elsevier, F. Hoffmann-La Roche, ICARE Schizophrenia, K. G. Jebsen Foundation, L.E.K Consulting, Lundbeck International Foundation (LINF), R. Adamczak, Roche Pharma, Science Foundation, Sumitomo Dainippon Pharma, Synapsis Foundation–Alzheimer Research Switzerland, and System Analytics, and has received lectures fees including travel fees from Boehringer Ingelheim, Fama Public Relations, Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Janssen-Cilag, Klinikum Christophsbad, Göppingen, Lilly Deutschland, Luzerner Psychiatrie, LVR Klinikum Düsseldorf, LWL Psychiatrie Verbund Westfalen-Lippe, Otsuka Pharmaceuticals, Reunions i Ciencia S. L., Spanish Society of Psychiatry, Südwestrundfunk Fernsehen, Stern TV, and Vitos Klinikum Kurhessen. WM has received lecture or travel fees from Pfizer, Grünenthal, University of Zürich, International Association for the Study on Pain (IASP), and European Federation of IASP Chapters (EFIC). SB discloses that he has in the last 5?years acted as an author, consultant or lecturer for Shire, Medice, Roche, Eli Lilly, Prima Psychiatry, GLGroup, System Analytic, Ability Partner, Kompetento, Expo Medica, Clarion Healthcare, and Prophase. He receives royalties for textbooks and diagnostic tools from Huber/Hogrefe, Kohlhammer, and UTB. The other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition with key deficits in social functioning. It is widely assumed that the biological underpinnings of social impairment are neurofunctional alterations in the "social brain," a neural circuitry involved in inferring the mental state of a social partner. However, previous evidence comes from small-scale studies and findings have been mixed. We therefore carried out the to-date largest study on neural correlates of mentalizing in ASD. METHODS: As part of the Longitudinal European Autism Project, we performed functional magnetic resonance imaging at six European sites in a large, well-powered, and deeply phenotyped sample of individuals with ASD (N = 205) and typically developing (TD) individuals (N = 189) aged 6 to 30?years. We presented an animated shapes task to assess and comprehensively characterize social brain activation during mentalizing. We tested for effects of age, diagnosis, and their association with symptom measures, including a continuous measure of autistic traits. RESULTS: We observed robust effects of task. Within the ASD sample, autistic traits were moderately associated with functional activation in one of the key regions of the social brain, the dorsomedial prefrontal cortex. However, there were no significant effects of diagnosis on task performance and no effects of age and diagnosis on social brain responses. Besides a lack of mean group differences, our data provide no evidence for meaningful differences in the distribution of brain response measures. Extensive control analyses suggest that the lack of case-control differences was not due to a variety of potential confounders. CONCLUSIONS: Contrary to prior reports, this large-scale study does not support the assumption that altered social brain activation during mentalizing forms a common neural marker of ASD, at least with the paradigm we employed. Yet, autistic individuals show socio-behavioral deficits. Our work therefore highlights the need to interrogate social brain function with other brain measures, such as connectivity and network-based approaches, using other paradigms, or applying complementary analysis approaches to assess individual differences in this heterogeneous condition. En ligne : http://dx.doi.org/10.1186/s13229-020-0317-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427
in Molecular Autism > 11 (2020) . - 17 p.[article] Social brain activation during mentalizing in a large autism cohort: the Longitudinal European Autism Project [Texte imprimé et/ou numérique] / Carolin MOESSNANG, Auteur ; Sarah BAUMEISTER, Auteur ; Julian TILLMANN, Auteur ; David GOYARD, Auteur ; Tony CHARMAN, Auteur ; Sara AMBROSINO, Auteur ; Simon BARON-COHEN, Auteur ; Christian F. BECKMANN, Auteur ; Sven BÖLTE, Auteur ; Carsten BOURS, Auteur ; Daisy CRAWLEY, Auteur ; Flavio DELL'ACQUA, Auteur ; Sarah DURSTON, Auteur ; Christine ECKER, Auteur ; Vincent FROUIN, Auteur ; Hannah HAYWARD, Auteur ; Rosemary HOLT, Auteur ; Mark H. JOHNSON, Auteur ; Emily JONES, Auteur ; Meng-Chuan LAI, Auteur ; Michael V. LOMBARDO, Auteur ; Luke MASON, Auteur ; Marianne OLDENHINKEL, Auteur ; Antonio PERSICO, Auteur ; Antonia SAN JOSE CACERES, Auteur ; Will SPOOREN, Auteur ; Eva LOTH, Auteur ; Declan G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Tobias BANASCHEWSKI, Auteur ; Daniel BRANDEIS, Auteur ; Heike TOST, Auteur ; Andreas MEYER-LINDENBERG, Auteur . - 17 p.
Langues : Anglais (eng)
in Molecular Autism > 11 (2020) . - 17 p.
Mots-clés : Animated shapes Autism Autism spectrum disorder Development Mentalizing Multi-site Social brain Theory of mind fMRI Science, Atheneum Partners, Blueprint Partnership, Boehringer Ingelheim, Daimler und Benz Stiftung, Elsevier, F. Hoffmann-La Roche, ICARE Schizophrenia, K. G. Jebsen Foundation, L.E.K Consulting, Lundbeck International Foundation (LINF), R. Adamczak, Roche Pharma, Science Foundation, Sumitomo Dainippon Pharma, Synapsis Foundation–Alzheimer Research Switzerland, and System Analytics, and has received lectures fees including travel fees from Boehringer Ingelheim, Fama Public Relations, Institut d’investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Janssen-Cilag, Klinikum Christophsbad, Göppingen, Lilly Deutschland, Luzerner Psychiatrie, LVR Klinikum Düsseldorf, LWL Psychiatrie Verbund Westfalen-Lippe, Otsuka Pharmaceuticals, Reunions i Ciencia S. L., Spanish Society of Psychiatry, Südwestrundfunk Fernsehen, Stern TV, and Vitos Klinikum Kurhessen. WM has received lecture or travel fees from Pfizer, Grünenthal, University of Zürich, International Association for the Study on Pain (IASP), and European Federation of IASP Chapters (EFIC). SB discloses that he has in the last 5?years acted as an author, consultant or lecturer for Shire, Medice, Roche, Eli Lilly, Prima Psychiatry, GLGroup, System Analytic, Ability Partner, Kompetento, Expo Medica, Clarion Healthcare, and Prophase. He receives royalties for textbooks and diagnostic tools from Huber/Hogrefe, Kohlhammer, and UTB. The other authors declare that they have no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Autism spectrum disorder (ASD) is a neurodevelopmental condition with key deficits in social functioning. It is widely assumed that the biological underpinnings of social impairment are neurofunctional alterations in the "social brain," a neural circuitry involved in inferring the mental state of a social partner. However, previous evidence comes from small-scale studies and findings have been mixed. We therefore carried out the to-date largest study on neural correlates of mentalizing in ASD. METHODS: As part of the Longitudinal European Autism Project, we performed functional magnetic resonance imaging at six European sites in a large, well-powered, and deeply phenotyped sample of individuals with ASD (N = 205) and typically developing (TD) individuals (N = 189) aged 6 to 30?years. We presented an animated shapes task to assess and comprehensively characterize social brain activation during mentalizing. We tested for effects of age, diagnosis, and their association with symptom measures, including a continuous measure of autistic traits. RESULTS: We observed robust effects of task. Within the ASD sample, autistic traits were moderately associated with functional activation in one of the key regions of the social brain, the dorsomedial prefrontal cortex. However, there were no significant effects of diagnosis on task performance and no effects of age and diagnosis on social brain responses. Besides a lack of mean group differences, our data provide no evidence for meaningful differences in the distribution of brain response measures. Extensive control analyses suggest that the lack of case-control differences was not due to a variety of potential confounders. CONCLUSIONS: Contrary to prior reports, this large-scale study does not support the assumption that altered social brain activation during mentalizing forms a common neural marker of ASD, at least with the paradigm we employed. Yet, autistic individuals show socio-behavioral deficits. Our work therefore highlights the need to interrogate social brain function with other brain measures, such as connectivity and network-based approaches, using other paradigms, or applying complementary analysis approaches to assess individual differences in this heterogeneous condition. En ligne : http://dx.doi.org/10.1186/s13229-020-0317-x Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=427 Towards robust and replicable sex differences in the intrinsic brain function of autism / D. L. FLORIS in Molecular Autism, 12 (2021)
[article]
Titre : Towards robust and replicable sex differences in the intrinsic brain function of autism Type de document : Texte imprimé et/ou numérique Auteurs : D. L. FLORIS, Auteur ; J. O. A. FILHO, Auteur ; Meng-Chuan LAI, Auteur ; S. GIAVASIS, Auteur ; M. OLDEHINKEL, Auteur ; M. MENNES, Auteur ; Tony CHARMAN, Auteur ; J. TILLMANN, Auteur ; G. DUMAS, Auteur ; C. ECKER, Auteur ; F. DELL'ACQUA, Auteur ; Tobias BANASCHEWSKI, Auteur ; C. MOESSNANG, Auteur ; Simon BARON-COHEN, Auteur ; S. DURSTON, Auteur ; E. LOTH, Auteur ; D. G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; M. P. MILHAM, Auteur ; A. DI MARTINO, Auteur Article en page(s) : 19 p. Langues : Anglais (eng) Mots-clés : Adolescent Autistic Disorder/diagnostic imaging/physiopathology Brain/diagnostic imaging/physiopathology Child Female Humans Magnetic Resonance Imaging Male Sex Characteristics Autism spectrum disorder Replication Resting-state functional connectivity Robustness Sex differences Voxel-mirrored homotopic connectivity Responsiveness Scale—Child Version by Organization Speciali, Italy. JKB has been a consultant to, advisory board member of, and a speaker for Takeda/Shire, Medice, Roche, 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, or royalties. CFB is director and shareholder in SBGneuro Ltd. TC has received consultancy from Roche and Servier and received book royalties from Guildford Press and Sage. DM has been a consultant to, and advisory board member, for Roche and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. TB served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm. He received conference support or speaker’s fee by Lilly, Medice, and Shire. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press the present work is unrelated to these relationships. JT is a consultant to Roche. The remaining authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data. METHODS: We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z?>?3.1, cluster-level P?0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research. RESULTS: Discovery analyses in ABIDE revealed significant main effects of diagnosis and sex across the intrinsic functional connectivity of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples-EU-AIMS LEAP. LIMITATIONS: Given the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability. CONCLUSIONS: Atypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies. En ligne : http://dx.doi.org/10.1186/s13229-021-00415-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459
in Molecular Autism > 12 (2021) . - 19 p.[article] Towards robust and replicable sex differences in the intrinsic brain function of autism [Texte imprimé et/ou numérique] / D. L. FLORIS, Auteur ; J. O. A. FILHO, Auteur ; Meng-Chuan LAI, Auteur ; S. GIAVASIS, Auteur ; M. OLDEHINKEL, Auteur ; M. MENNES, Auteur ; Tony CHARMAN, Auteur ; J. TILLMANN, Auteur ; G. DUMAS, Auteur ; C. ECKER, Auteur ; F. DELL'ACQUA, Auteur ; Tobias BANASCHEWSKI, Auteur ; C. MOESSNANG, Auteur ; Simon BARON-COHEN, Auteur ; S. DURSTON, Auteur ; E. LOTH, Auteur ; D. G. M. MURPHY, Auteur ; Jan K. BUITELAAR, Auteur ; Christian F. BECKMANN, Auteur ; M. P. MILHAM, Auteur ; A. DI MARTINO, Auteur . - 19 p.
Langues : Anglais (eng)
in Molecular Autism > 12 (2021) . - 19 p.
Mots-clés : Adolescent Autistic Disorder/diagnostic imaging/physiopathology Brain/diagnostic imaging/physiopathology Child Female Humans Magnetic Resonance Imaging Male Sex Characteristics Autism spectrum disorder Replication Resting-state functional connectivity Robustness Sex differences Voxel-mirrored homotopic connectivity Responsiveness Scale—Child Version by Organization Speciali, Italy. JKB has been a consultant to, advisory board member of, and a speaker for Takeda/Shire, Medice, Roche, 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, or royalties. CFB is director and shareholder in SBGneuro Ltd. TC has received consultancy from Roche and Servier and received book royalties from Guildford Press and Sage. DM has been a consultant to, and advisory board member, for Roche and Servier. He is not an employee of any of these companies, and not a stock shareholder of any of these companies. TB served in an advisory or consultancy role for Lundbeck, Medice, Neurim Pharmaceuticals, Oberberg GmbH, Shire, and Infectopharm. He received conference support or speaker’s fee by Lilly, Medice, and Shire. He received royalties from Hogrefe, Kohlhammer, CIP Medien, Oxford University Press the present work is unrelated to these relationships. JT is a consultant to Roche. The remaining authors declare no competing interests. Index. décimale : PER Périodiques Résumé : BACKGROUND: Marked sex differences in autism prevalence accentuate the need to understand the role of biological sex-related factors in autism. Efforts to unravel sex differences in the brain organization of autism have, however, been challenged by the limited availability of female data. METHODS: We addressed this gap by using a large sample of males and females with autism and neurotypical (NT) control individuals (ABIDE; Autism: 362 males, 82 females; NT: 409 males, 166 females; 7-18 years). Discovery analyses examined main effects of diagnosis, sex and their interaction across five resting-state fMRI (R-fMRI) metrics (voxel-level Z?>?3.1, cluster-level P?0.01, gaussian random field corrected). Secondary analyses assessed the robustness of the results to different pre-processing approaches and their replicability in two independent samples: the EU-AIMS Longitudinal European Autism Project (LEAP) and the Gender Explorations of Neurogenetics and Development to Advance Autism Research. RESULTS: Discovery analyses in ABIDE revealed significant main effects of diagnosis and sex across the intrinsic functional connectivity of the posterior cingulate cortex, regional homogeneity and voxel-mirrored homotopic connectivity (VMHC) in several cortical regions, largely converging in the default network midline. Sex-by-diagnosis interactions were confined to the dorsolateral occipital cortex, with reduced VMHC in females with autism. All findings were robust to different pre-processing steps. Replicability in independent samples varied by R-fMRI measures and effects with the targeted sex-by-diagnosis interaction being replicated in the larger of the two replication samples-EU-AIMS LEAP. LIMITATIONS: Given the lack of a priori harmonization among the discovery and replication datasets available to date, sample-related variation remained and may have affected replicability. CONCLUSIONS: Atypical cross-hemispheric interactions are neurobiologically relevant to autism. They likely result from the combination of sex-dependent and sex-independent factors with a differential effect across functional cortical networks. Systematic assessments of the factors contributing to replicability are needed and necessitate coordinated large-scale data collection across studies. En ligne : http://dx.doi.org/10.1186/s13229-021-00415-z Permalink : https://www.cra-rhone-alpes.org/cid/opac_css/index.php?lvl=notice_display&id=459