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Stratifying the autistic phenotype using electrophysiological indices of social perception

Research output: Contribution to journalArticlepeer-review

Luke Mason, Carolin Moessnang, Christopher Chatham, Lindsay Ham, Julian Tillmann, Guillaume Dumas, Claire Ellis, Claire S. Leblond, Freddy Cliquet, Thomas Bourgeron, Christian Beckmann, Tony Charman, Beth Oakley, Tobias Banaschewski, Andreas Meyer-Lindenberg, Simon Baron-Cohen, Sven Bölte, Jan K. Buitelaar, Sarah Durston, Eva Loth & 7 more Bob Oranje, Antonio Persico, Flavio Dell'Acqua, Christine Ecker, Mark H. Johnson, Declan Murphy, Emily J.H. Jones

Original languageEnglish
Article numbereabf8987
Pages (from-to)eabf8987
JournalScience translational medicine
Issue number658
Accepted/In press21 Mar 2022
Published17 Aug 2022

Bibliographical note

Funding Information: Many thanks to the participants of the LEAP study and all members of the AIMS2 and EUAIMS consortia, including J. Ahmad, S. Ambrosino, S. Baumeister, C. Bours, C. Brogna, Y. de Bruijn, I. Cornelissen, D. Crawley, J. Faulkner, V. Frouin, P. Garces, D. Goyard, J. Hipp, R. Holt, M.-C. Lai, D. J. Lythgoe, R. Mandl, M. Mennes, A. Meyer-Lindenberg, N. Bast, L. O’Dwyer, M. Oldehinkel, G. Pandina, B. Ruggeri, A. Ruigrok, J. Sabet, R. Sacco, A. San José Cáceres, E. Simonoff, W. Spooren, R. Toro, H. Tost, J. Waldman, C. Wooldridge, and M. P. Zwiers. This project has received funding from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115300, resources of which are composed of financial contribution from the European Union’s Seventh Framework Programme (FP7/2007–2013) and EFPIA companies’ in kind contribution (E.J.H.J., M.J., T.C., and D.M.), and the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement no. 777394 (E.J.H.J., M.J., T.C., and D.M.). This Joint Undertaking receives support from the European Union’s Horizon 2020 research and innovation program and EFPIA and AUTISM SPEAKS, Autistica, SFARI; awards from the Medical Research Council (MR/K021389/1; MR/T003057/1; E.J.H.J., M.J., and T.C.). Publisher Copyright: © 2022 The Authors, some rights reserved.

King's Authors


Autism spectrum disorder (ASD) is a neurodevelopmental condition characterized by difficulties in social communication, but also great heterogeneity. To offer individualized medicine approaches, we need to better target interventions by stratifying autistic people into subgroups with different biological profiles and/or prognoses. We sought to validate neural responses to faces as a potential stratification factor in ASD by measuring neural (electroencephalography) responses to faces (critical in social interaction) in N = 436 children and adults with and without ASD. The speed of early-stage face processing (N170 latency) was on average slower in ASD than in age-matched controls. In addition, N170 latency was associated with responses to faces in the fusiform gyrus, measured with functional magnetic resonance imaging, and polygenic scores for ASD. Within the ASD group, N170 latency predicted change in adaptive socialization skills over an 18-month follow-up period; data-driven clustering identified a subgroup with slower brain responses and poor social prognosis. Use of a distributional data-driven cutoff was associated with predicted improvements of power in simulated clinical trials targeting social functioning. Together, the data provide converging evidence for the utility of the N170 as a stratification factor to identify biologically and prognostically defined subgroups in ASD.

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