Les sous-types de comportement social-communicatif déséquilibré et de comportement répétitif restreint du "trouble du spectre de l'autisme" présentent des circuits neuronaux différents

Aperçu: G.M.

La communication sociale (SC) et les comportements répétitifs restreints (CRR) sont des domaines de symptômes diagnostiques de l'autisme. La gravité de la SC et du CRRpeut différer considérablement au sein et entre les individus et peut être étayée par différents circuits neuronaux et mécanismes génétiques.
La modélisation de l'équilibre SC-RRB pourrait aider à identifier comment les circuits neuronaux et les mécanismes génétiques correspondent à une telle hétérogénéité phénotypique. 

Ici, nous avons développé un modèle de stratification phénotypique qui permet des prédictions de sous-types SC = CRR, SC> CRR et CRR> SC très précises (97-99%) hors échantillon. En appliquant ce modèle aux données IRMf à l'état de repos de l'ensemble de données EU-AIMS LEAP (n = 509), nous constatons que si les sous-types phénotypiques partagent de nombreux points communs en termes de connectivité fonctionnelle intrinsèque, ils montrent également des différences réplicables au sein de certains réseaux par rapport à un groupe au développement typique (DT).
Plus précisément, le réseau somatomoteur est hypoconnecté avec les circuits périsylviens en SC> CRR et les circuits d'association visuelle en SC = CRR. Le sous-type SC = CRR montre une hyperconnectivité entre le moteur médial et les circuits de saillance antérieure.
Les gènes qui sont fortement exprimés dans ces réseaux montrent un modèle d'enrichissement différentiel avec des gènes connus associés à l'autisme, indiquant que ces circuits sont affectés par différents mécanismes génomiques associés à l'autisme. 

Ces résultats suggèrent que les sous-types de déséquilibre SC-CRR partagent de nombreux points communs, mais expriment également des différences subtiles dans les circuits neuronaux fonctionnels et les fondements génomiques derrière ces circuits. 

. 2021 May 14;4(1):574. doi: 10.1038/s42003-021-02015-2.

Imbalanced social-communicative and restricted repetitive behavior subtypes of autism spectrum disorder exhibit different neural circuitry

Natasha Bertelsen  ^{1   2} , Isotta Landi  ¹ , Richard A I Bethlehem  ³ , Jakob Seidlitz  ^{4   5} , Elena Maria Busuoli  ^{1   2} , Veronica Mandelli  ^{1   2} , Eleonora Satta  ¹ , Stavros Trakoshis  ^{1   6} , Bonnie Auyeung  ^{7   8} , Prantik Kundu  ⁹ , Eva Loth  ^{10   11} , Guillaume Dumas  ¹² , Sarah Baumeister  ¹³ , Christian F Beckmann  ¹⁴ , Sven Bölte  ^{15   16   17} , Thomas Bourgeron  ¹² , Tony Charman  ¹⁸ , Sarah Durston  ¹⁹ , Christine Ecker  ²⁰ , Rosemary J Holt  ⁸ , Mark H Johnson  ²¹ , Emily J H Jones  ²² , Luke Mason  ²² , Andreas Meyer-Lindenberg  ²³ , Carolin Moessnang  ²³ , Marianne Oldehinkel  ^{14   24} , Antonio M Persico  ^{25   26} , Julian Tillmann  ^{18   27} , Steve C R Williams  ²⁸ , Will Spooren  ²⁹ , Declan G M Murphy  ^{10   11} , Jan K Buitelaar  ¹⁴ , EU-AIMS LEAP group; Simon Baron-Cohen  ⁸ , Meng-Chuan Lai  ^{8   30   31   32   33} , Michael V Lombardo  ^{34   35}

Collaborators, Affiliations

• PMID: 33990680
• DOI: 10.1038/s42003-021-02015-2

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 > 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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