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Face–brain asymmetry in autism spectrum disorders

Molecular Psychiatry volume 13, pages 614–623 (2008)Cite this article

Abstract

The heterogeneity of autism spectrum disorders (ASDs) confounds attempts to identify causes and pathogenesis. Identifiable endophenotypes and reliable biomarkers within ASDs would help to focus molecular research and uncover genetic causes and developmental mechanisms. We used dense surface-modelling techniques to compare the facial morphology of 72 boys with ASD and 128 first-degree relatives to that of 254 unrelated controls. Pattern-matching algorithms were able to discriminate between the faces of ASD boys and those of matched controls (AUC=0.82) and also discriminate between the faces of unaffected mothers of ASD children and matched female controls (AUC=0.76). We detected significant facial asymmetry in boys with ASD (P<0.01), notably depth-wise in the supra- and periorbital regions anterior to the frontal pole of the right hemisphere of the brain. Unaffected mothers of children with ASD display similar significant facial asymmetry, more exaggerated than that in matched controls (P<0.03) and, in particular, show vertical asymmetry of the periorbital region. Unaffected fathers of children with ASD did not show facial asymmetry to a significant degree compared to controls. Two thirds of unaffected male siblings tested were classified unseen as more facially similar to unrelated boys with ASD than to unrelated controls. These unaffected male siblings and two small groups of girls with ASD and female siblings, all show overall directional asymmetry, but without achieving statistical significance in two-tailed t-tests of individual asymmetry of ASD family and matched control groups. We conclude that previously identified right dominant asymmetry of the frontal poles of boys with ASD could explain their facial asymmetry through the direct effect of brain growth. The atypical facial asymmetry of unaffected mothers of children with ASD requires further brain studies before the same explanation can be proposed. An alternative explanation, not mutually exclusive, is a simultaneous and parallel action on face and brain growth by genetic factors. Both possibilities suggest the need for coordinated face and brain studies on ASD probands and their first-degree relatives, especially on unaffected mothers, given that their unusual facial asymmetry suggests an ASD susceptibility arising from maternal genes.

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Acknowledgements

This project was supported by operative funding from NewLife (PH), Fogarty/NIH (R21TW06761-01; PH); National Alliance for Autism Research-Autism Speaks (PH, MESL); the Canadian Institutes for Health Research (IHRT 43820, JJAH; no. RT-64217, MESL) and Canada Foundation for Innovation (no. 7939, JJAH). MESL is a Career Scholar funded by the Michael Smith Foundation for Health Research. We thank the families who volunteered for face scanning and the assistance of MJ Hildebrand and L Kasmara. Professors Andrew Wilkie, David Skuse and Annette Karmiloff-Smith provided helpful comments on early drafts of the manuscript. Dr Henry Potts and Dr Anthony Kinsella provided valuable comments on statistical analyses. We also thank the anonymous referees whose constructive criticism has resulted in significant improvements to the content, clarity and organization of the paper.

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Authors and Affiliations

  1. Eastman Dental Institute, UCL, London, UK

    P Hammond & T J Hutton

  2. Institute of Child Health, UCL, London, UK

    P Hammond

  3. Queen's University, Kingston, ON, Canada

    C Forster-Gibson, J McKenzie & J J A Holden

  4. Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, MB, Canada

    A E Chudley

  5. Department of Genetics, Children's Hospital of Eastern Ontario, University of Ottawa, Ottawa, ON, Canada

    J E Allanson

  6. The Credit Valley Hospital, Mississauga, ON, Canada

    S A Farrell

  7. Department of Medical Genetics, Child and Family Research Institute, University of British Columbia, Vancouver, BC, Canada

    M E S Lewis

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  1. P Hammond
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  9. M E S Lewis
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Corresponding authors

Correspondence to P Hammond or M E S Lewis.

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Supplementary Information accompanies the paper on the Molecular Psychiatry website (http://www.nature.com/mp)

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Hammond, P., Forster-Gibson, C., Chudley, A. et al. Face–brain asymmetry in autism spectrum disorders. Mol Psychiatry 13, 614–623 (2008). https://doi.org/10.1038/mp.2008.18

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