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Dissecting the heterogeneous cortical anatomy of autism spectrum disorder using normative models.

Research output: Contribution to journalArticle

Mariam Zabihi, Marianne Oldehinkel, Thomas Wolfers, Vincent Frouin, David Goyard, Eva Loth, Tony Charman, Julian Tillmann, Tobias Banaschewski, Guillaume Dumas, Rosemary Holt, Simon Baron-Cohen, Sarah Durston, Sven Bölte, Declan Murphy, Christine Ecker, Jan K. Buitelaar, Christian F. Beckmann, Andre F. Marquand

Original languageEnglish
JournalBiological Psychiatry: Cognitive Neuroscience and Neuroimaging
Early online date19 Dec 2018
Publication statusE-pub ahead of print - 19 Dec 2018


King's Authors


Background The neuroanatomical basis of autism spectrum disorder (ASD) has remained elusive, mostly due to high biological and clinical heterogeneity among diagnosed individuals. Despite considerable effort towards understanding ASD using neuroimaging biomarkers, heterogeneity remains a barrier, partly because studies mostly employ case-control approaches, which assume that the clinical group is homogeneous. Methods Here, we used an innovative normative modelling approach to parse biological heterogeneity in ASD. We aimed to dissect the neuroanatomy of ASD by mapping the deviations from a typical pattern of neuroanatomical development at the level of the individual and to show the necessity to look beyond the case-control paradigm to understand the neurobiology of ASD. We first estimated a vertex-wise normative model of cortical thickness development using Gaussian process regression, then mapped the deviation of each participant from the typical pattern. For this we employed a heterogeneous cross-sectional sample of 206 typically developing (TD) individuals (127 male), and 321 individuals (232 male) with ASD (aged 6-31). Results We found few case-control differences but the ASD cohort showed highly individualized patterns of deviations in cortical thickness that were widespread across the brain. These deviations correlated with severity of repetitive behaviors and social communicative symptoms, although only repetitive behaviors survived corrections for multiple testing. Conclusions Our results: (i) reinforce the notion that individuals with ASD show distinct, highly individualized trajectories of brain development and (ii) show that by focusing on common effects (i.e. the ‘average ASD participant’), the case-control approach disguises considerable inter-individual variation crucial for precision medicine.

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