18713
Cerebellum Enlargement in 4-6-Month-Old Infants at High Familial Risk of Autism Spectrum Disorders

Thursday, May 14, 2015: 5:30 PM-7:00 PM
Imperial Ballroom (Grand America Hotel)
I. Pote1, S. Wang2, A. Blasi3, T. Charman4, E. Daly1, M. H. Johnson3, M. Kuklisova-Murgasova5, S. Lloyd-Fox3, E. Mercure6, V. Sethna1, S. Williams7, D. G. Murphy1 and G. M. McAlonan1, (1)Department of Forensic and Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom, (2)Department of Engineering Science, Institute of Biomedical Engineering, University of Oxford, Oxford, United Kingdom, (3)Centre for Brain and Cognitive Development, Birkbeck, University of London, London, United Kingdom, (4)Department of Psychology, Henry Wellcome Building, King's College London, London, United Kingdom, (5)Division of Imaging Sciences and Biomedical Engineering, King's College London, London, United Kingdom, (6)University College London, Institute of Cognitive Neuroscience, London, United Kingdom, (7)Department of Neuroimaging, Institute of Psychiatry, Psychology & Neuroscience, King's College London, London, United Kingdom
Background:  Imaging studies of typical brain development highlight that the first two years of life are a time of dynamic growth. However, very little is known about early brain development in infants at high familial risk of autism spectrum disorder (ASD), prior to the age of two. At present, only two other groups have studied high-risk infants at 6-months of age, with one group finding no significant differences in intracranial, cerebrum, cerebellum or lateral ventricular volume (Hazlett et al., 2012), and the other finding significant enlargements in total brain volume and extra-axial fluid (Shen et al., 2013).

Objectives: In this study, magnetic resonance imaging (MRI) was used to investigate the differences in regional brain volumes from a sample of 4-6-month-old infants at high-risk of ASD, relative to a group of infants at low-risk. Infants were considered to be at 'high-risk' if they had an older sibling with a diagnosis of ASD, and at 'low-risk' if they had an older sibling who was typically-developing.

Methods: 31 (n=22 'high-risk', n=9 'low-risk') infants were scanned in natural sleep at 4-6-months of age on a 1.5T scanner. T2-weighted structural MRI images were acquired. The images were volumetrically segmented following an in-house automated protocol, which was based on the intensity distributions of the regions of interest, and made use of a probabilistic atlas. Following this, manual editing was carried out 'blind' to participant group. The intracranial, subcortical grey, total cerebrospinal fluid, cerebellum, midbrain, and lateral ventricular volumes were compared between groups, using a General Linear Model. The analysis was conducted on SPSS v.21, and the model controlled for age and gender.

Results: We found a significant group difference in the cerebellar volume [F(1,23)=4.420, p=0.047], with the infants at high-risk of ASD showing a significantly greater volume than those at low-risk. In addition, we also found a significant group by age interaction [F(1,23)=4.307, p=0.049], which was explained by a distinct relationship between age and cerebellar volume in infants at high-risk of ASD (r=0.807, p=0.0001), relative to those at low-risk (r=0.771, p=0.015). Between the ages of 120-150 days, infants at high-risk of ASD show larger cerebellar volumes that those at low-risk. However, by the age of 160 days, this pattern seems to be reversed (Figure 1). No other significant results were found. 

Conclusions: We emphasize that these results are preliminary and that data acquisition is still in progress. Nevertheless, this data suggests that within the first 6 months of life there are differences in the trajectory of cerebellar growth in infants at high-risk of ASD, relative to those at low-risk. Besides continuing with data acquisition, we are following up our participants until at least 3-4 years of age. We hope, eventually, to identify patterns of brain development before 6 months of age which signpost the future diagnosis of ASD in those infants at high familial risk.

See more of: Early Development (<48 months)
See more of: Early Development (< 48 months)