Uncovering neurodevelopmental paths to autism spectrum disorder through an integrated analysis of developmental measures and neural sensitivity to faces

Uncovering neurodevelopmental paths to autism spectrum disorder through an integrated analysis of developmental measures and neural sensitivity to faces

J Psychiatry Neurosci 2021;46(1):E34-E43 | PDF | Appendix

Giorgia Bussu, PhD; Alberto Llera, PhD; Emily J.H. Jones, PhD; Charlotte Tye, PhD; Tony Charman, PhD; Mark H. Johnson, PhD; Christian F. Beckmann, PhD; Jan K. Buitelaar, PhD

Background: Autism spectrum disorder (ASD) is highly heterogeneous in its etiology and manifestation. The neurobiological processes underlying ASD development are reflected in multiple features, from behaviour and cognition to brain functioning. An integrated analysis of these features may optimize the identification of these processes.

Methods: We examined cognitive and adaptive functioning and ASD symptoms between 8 and 36 months in 161 infants at familial high risk for ASD and 71 low-risk controls; we also examined neural sensitivity to eye gaze at 8 months in a subsample of 140 high-risk and 61 low-risk infants. We used linked independent component analysis to extract patterns of variation across domains and development, and we selected the patterns significantly associated with clinical classification at 36 months.

Results: An early process at 8 months, indicating high levels of functioning and low levels of symptoms linked to higher attention to gaze shifts, was reduced in infants who developed ASD. A longitudinal process of increasing functioning and low levels of symptoms was reduced in infants who developed ASD, and another process suggesting a stagnation in cognitive functioning at 24 months was increased in infants who developed ASD.

Limitations: Although the results showed a clear significant trend relating to clinical classification, we found substantial overlap between groups.

Conclusion: We uncovered underlying processes that acted together early in development and were associated with clinical outcomes. Our results highlighted the complexity of emerging ASD, which goes beyond the borders of clinical categories. Future work should integrate genetic data to investigate the specific genetic risks linked to these processes.


Submitted Sep. 3, 2019; Revised Jan. 19, 2020; Accepted Feb. 25, 2020; Early-released Sept. 24, 2020

Acknowledgements: The authors thank all the individuals and families who participated in this research. They also thank the researchers from the BASIS team for data collection: Anna Blasi, Simon Baron-Cohen, Rachael Bedford, Patrick Bolton, Susie Chandler, Celeste Cheung, Kim Davies, Janice Fernandes, Isobel Gammer, Anna Gui, Kristelle Hudry, Evelyne Mercure, Sarah Lloyd-Fox, Louise O’Hara, Greg Pasco, Andrew Pickles, Helena Ribeiro, Erica Salomone, Leslie Tucker, Agnes Volein.

Affiliations: From the Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, the Netherlands (Bussu, Llera, Buitelaar, Beckmann); the Centre for Brain and Cognitive Development, Birkbeck College, University of London, London, UK (Jones, Johnson); the Department of Child & Adolescent Psychiatry and MRC Social, Genetic & Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, UK (Tye); and the Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, UK; South London and Maudsley NHS Foundation Trust (SLaM), London, UK (Charman).

Competing interests: G. Bussu reports a grant from the European Community’s Horizon 2020 Program (Brainview) during the conduct of this study. E. Jones reports grants from the European Community’s Horizon 2020 Program (Brainview and EU AIMS) and the UK Medical Research Council during the conduct of this study. T. Charman reports grants from the UK Medical Research Council and the Innovative Medicines Initiative during the conduct of the study, as well as personal fees from Hoffmann-La Roche Ltd, Sage Publications and Guilford Publications, outside the submitted work. C. Beckmann is the co-founder, director and shareholder of SBGneuro Ltd. No other competing interests were declared.

Contributors: G. Bussu, A. Llera, E. Jones, T. Charman, M. Johnson, C. Beckman and J. Buitelaar designed the study. C. Tye acquired the data, which G. Bussu, A. Llera, E. Jones, T. Charman, M. Johnson, C. Beckman and J. Buitelaar analyzed. G. Bussu wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.

Content licence: This is an Open Access article distributed in accordance with the terms of the Creative Commons Attribution (CC BY-NC-ND 4.0) licence, which permits use, distribution and reproduction in any medium, provided that the original publication is properly cited, the use is non-commercial (i.e. research or educational use), and no modifications or adaptations are made. See: https://creativecommons.org/licenses/by-nc-nd/4.0/

DOI: 10.1503/jpn.190148

Correspondence to: G. Bussu, Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Kapittelweg 29, 6525 EN Nijmegen, Netherlands; g.bussu@donders.ru.nl