Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry
Creators: name: Bertelsen, Natasha
name: Landi, Isotta
name: Bethlehem, Richard A. I.
name: Seidlitz, Jakob
name: Busuoli, Elena Maria
name: Mandelli, Veronica
name: Satta, Eleonora
name: Trakoshis, Stavros
name: Auyeung, Bonnie
name: Kundu, Prantik
name: Loth, Eva
name: Dumas, Guillaume
name: Baumeister, Sarah
name: Beckmann, Christian F.
name: Bölte, Sven
name: Bourgeron, Thomas
name: Charman, Tony
name: Durston, Sarah
name: Ecker, Christine
name: Holt, Rosemary J.
name: Johnson, Mark H.
name: Jones, Emily J. H.
name: Mason, Luke
name: Meyer-Lindenberg, Andreas
name: Moessnang, Carolin
name: Oldehinkel, Marianne
name: Tillmann, Julian
name: Williams, Steve C. R.
name: Spooren, Will
name: Murphy, Declan G. M.
name: Buitelaar, Jan K.
name: Baron-Cohen, Simon
name: Lai, Meng-Chuan
name: Lombardo, Michael V.
name: Ahmad, Jumana
name: Ambrosino, Sara
name: Banaschewski, Tobias
name: Bours, Carsten
name: Brammer, Michael
name: Brandeis, Daniel
name: Brogna, Claudia
name: De Bruijn, Yvette
name: Chakrabarti, Bhismadev
name: Chatham, Chris
name: Cornelissen, Ineke
name: Crawley, Daisy
name: Dell’Acqua, Flavio
name: Faulkner, Jessica
name: Frouin, Vincent
name: Garcés, Pilar
name: Goyard, David
name: Ham, Lindsay
name: Hayward, Hannah
name: Hipp, Joerg
name: D’ardhuy, Xavier Liogier
name: Lythgoe, David J.
name: Mandl, René
name: Marquand, Andre
name: Mennes, Maarten
name: Mueller, Nico
name: Oakley, Bethany
name: O’Dwyer, Laurence
name: Oranje, Bob
name: Pandina, Gahan
name: Persico, Antonio M.
name: Ruggeri, Barbara
name: Ruigrok, Amber N. V.
name: Sabet, Jessica
name: Sacco, Roberto
name: Cáceres, Antonia San José
name: Simonoff, Emily
name: Toro, Roberto
name: Tost, Heike
name: Waldman, Jack
name: Wooldridge, Caroline
name: Zwiers, Marcel P.
Publisher: name: Apollo - University of Cambridge Repository
Year: 2021
Subjects: Article
/631/378/1689/1373
/692/699/476/1373
/59
/59/36
article

description: Abstract: 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 &gt; RRB, and RRB &gt; 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 &gt; 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.