Familial risk of autism alters subcortical and cerebellar brain anatomy in infants and predicts the emergence of repetitive behaviors in early childhood

Pote, Inês; Wang, Siying; Sethna, Vaheshta; Blasi, Anna; Daly, Eileen; Kuklisova‐Murgasova, Maria; Lloyd‐Fox, Sarah; Mercure, Evelyne; Busuulwa, Paula; Stoencheva, Vladimira; Charman, Tony; Williams, Steven C. R.; Johnson, Mark H.; Murphy, Declan G. M. and McAlonan, Grainne M.. 2019. Familial risk of autism alters subcortical and cerebellar brain anatomy in infants and predicts the emergence of repetitive behaviors in early childhood. Autism Research, 12(4), pp. 614-627. ISSN 1939-3792 [Article]

Pote_et_al-2019-Autism_Research.pdf - Published Version
Available under License Creative Commons Attribution.

Download (518kB) | Preview

Abstract or Description

Autism spectrum disorder (ASD) is a common neurodevelopmental condition, and infant siblings of children with ASD are at a higher risk of developing autistic traits or an ASD diagnosis, when compared to those with typically developing siblings. Reports of differences in brain anatomy and function in high‐risk infants which predict later autistic behaviors are emerging, but although cerebellar and subcortical brain regions have been frequently implicated in ASD, no high‐risk study has examined these regions. Therefore, in this study, we compared regional MRI volumes across the whole brain in 4–6‐month‐old infants with (high‐risk, n = 24) and without (low‐risk, n = 26) a sibling with ASD. Within the high‐risk group, we also examined whether any regional differences observed were associated with autistic behaviors at 36 months. We found that high‐risk infants had significantly larger cerebellar and subcortical volumes at 4–6‐months of age, relative to low‐risk infants; and that larger volumes in high‐risk infants were linked to more repetitive behaviors at 36 months. Our preliminary observations require replication in longitudinal studies of larger samples. If correct, they suggest that the early subcortex and cerebellum volumes may be predictive biomarkers for childhood repetitive behaviors.

Item Type:


Identification Number (DOI):


Additional Information:

Lay Summary: Individuals with a family history of autism spectrum disorder (ASD) are at risk of ASD and related developmental difficulties. This study revealed that 4–6‐month‐old infants at high‐risk of ASD have larger cerebellum and subcortical volumes than low‐risk infants, and that larger volumes in high‐risk infants are associated with more repetitive behaviors in childhood.

This paper represents independent research part funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King's College London (Medical Research Council grant no. G0400061 to DGMM). This work was also supported by a Medical Research Council (MRC) Program Grant (no. G0701484 to MHJ), the Simons Foundation (grant no. SFARI201287 to MHJ), the BASIS funding consortium led by Autistica (www.basisnetwork.org), the developing human connectome project (dHCP) under the European Union's Seventh Framework Programme (grant FP7/2007‐2013; ERC grant agreement no. 319456), EU‐AIMS, and AIMS‐2 TRIALS. EU‐AIMS receives support from the Innovative Medicines Initiative (IMI) Joint Undertaking (JU) under grant agreement no. 115300, the resources of which are composed of financial contributions from the European Union's Seventh Framework Programme (grant FP7/2007‐2013), from the European Federation of Pharmaceutical Industries and Associations (EFPIA) companies' in‐kind contributions, and from Autism Speaks. AIMS‐2 TRIALS received funding from the IMI 2 JU under grant agreement no. 777394, with support from the European Union's Horizon 2020 research and innovation programme, EFPIA, AUTISM SPEAKS, Autistica, and SFARI. DGMM, GMM, TC, SCRW, and MJ are all part of the EU‐AIMS consortium. DGMM and GMM also receive support from the Sackler Centre for Translational Neurodevelopment at King's College London. MHJ, TC, AB, and SLF are additionally supported by the UK Medical Research Council. SCRW is additionally funded by the Wellcome Trust.


autism spectrum disorder, infants, familial risk, magnetic resonance imaging—structural, cerebellum, subcortex, mother–infant interaction

Departments, Centres and Research Units:



28 January 2019Accepted
22 February 2019Published Online
5 April 2019Published

Item ID:


Date Deposited:

10 Oct 2019 09:59

Last Modified:

11 Jun 2021 12:00

Peer Reviewed:

Yes, this version has been peer-reviewed.



View statistics for this item...

Edit Record Edit Record (login required)