Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry
Social-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify h...
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| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
14 May 2021
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| In: |
Communications biology
Year: 2021, Jahrgang: 4, Pages: 1-13 |
| ISSN: | 2399-3642 |
| DOI: | 10.1038/s42003-021-02015-2 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s42003-021-02015-2 Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s42003-021-02015-2 
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| Verfasserangaben: | Natasha Bertelsen, Isotta Landi, Richard A.I. Bethlehem, Jakob Seidlitz, Elena Maria Busuoli, Veronica Mandelli, Eleonora Satta, Stavros Trakoshis, Bonnie Auyeung, Prantik Kundu, Eva Loth, Guillaume Dumas, Sarah Baumeister, Christian F. Beckmann, Sven Bölte, Thomas Bourgeron, Tony Charman, Sarah Durston, Christine Ecker, Rosemary J. Holt, Mark H. Johnson, Emily J.H. Jones, Luke Mason, Andreas Meyer-Lindenberg, Carolin Moessnang, Marianne Oldehinkel, Antonio M. Persico, Julian Tillmann, Steve C.R. Williams, Will Spooren, Declan G.M. Murphy, Jan K. Buitelaar, Simon Baron-Cohen, Meng-Chuan Lai and Michael V. Lombardo |
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| 245 | 1 | 0 | |a Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry |c Natasha Bertelsen, Isotta Landi, Richard A.I. Bethlehem, Jakob Seidlitz, Elena Maria Busuoli, Veronica Mandelli, Eleonora Satta, Stavros Trakoshis, Bonnie Auyeung, Prantik Kundu, Eva Loth, Guillaume Dumas, Sarah Baumeister, Christian F. Beckmann, Sven Bölte, Thomas Bourgeron, Tony Charman, Sarah Durston, Christine Ecker, Rosemary J. Holt, Mark H. Johnson, Emily J.H. Jones, Luke Mason, Andreas Meyer-Lindenberg, Carolin Moessnang, Marianne Oldehinkel, Antonio M. Persico, Julian Tillmann, Steve C.R. Williams, Will Spooren, Declan G.M. Murphy, Jan K. Buitelaar, Simon Baron-Cohen, Meng-Chuan Lai and Michael V. Lombardo |
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| 520 | |a Social-communication (SC) and restricted repetitive behaviors (RRB) are autism diagnostic symptom domains. SC and RRB severity can markedly differ within and between individuals and may be underpinned by different neural circuitry and genetic mechanisms. Modeling SC-RRB balance could help identify how neural circuitry and genetic mechanisms map onto such phenotypic heterogeneity. Here, we developed a phenotypic stratification model that makes highly accurate (97-99%) out-of-sample SC = RRB, SC > RRB, and RRB > SC subtype predictions. Applying this model to resting state fMRI data from the EU-AIMS LEAP dataset (n = 509), we find that while the phenotypic subtypes share many commonalities in terms of intrinsic functional connectivity, they also show replicable differences within some networks compared to a typically-developing group (TD). Specifically, the somatomotor network is hypoconnected with perisylvian circuitry in SC > RRB and visual association circuitry in SC = RRB. The SC = RRB subtype show hyperconnectivity between medial motor and anterior salience circuitry. Genes that are highly expressed within these networks show a differential enrichment pattern with known autism-associated genes, indicating that such circuits are affected by differing autism-associated genomic mechanisms. These results suggest that SC-RRB imbalance subtypes share many commonalities, but also express subtle differences in functional neural circuitry and the genomic underpinnings behind such circuitry. | ||
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