31492
Longitudinal Sex Differences in Early Brain Growth in Autism Spectrum Disorder

Poster Presentation
Friday, May 3, 2019: 11:30 AM-1:30 PM
Room: 710 (Palais des congres de Montreal)
J. K. Lee1, D. S. Andrews1, A. L. Hechtman2, M. Solomon3, S. Rogers1, S. Ozonoff2, D. G. Amaral1 and C. W. Nordahl1, (1)Department of Psychiatry and Behavioral Sciences, The Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, UC Davis School of Medicine, University of California Davis, Sacramento, CA, (2)Psychiatry and Behavioral Sciences, University of California at Davis, MIND Institute, Sacramento, CA, (3)Department of Psychiatry & Behavioral Sciences, The Medical Investigation of Neurodevelopmental Disorders (MIND) Institute, University of California, Davis, Sacramento, CA
Background: Atypical growth patterns of total brain volume during childhood have been reported in ASD. However, longitudinal studies are lacking, and most existing studies reflect the male bias of ASD. Thus, sex differences in early brain enlargement and growth trajectories have not been fully explored.

Objectives: This longitudinal research examines sex differences in the growth of total cerebral volume (TCV) from early to middle childhood in ASD relative to age- and sex-matched typically developing (TD) controls.

Methods: The longitudinal sample comprised three annual time points spanning early childhood with 237 ASD (77 female) and 115 TD (52 female) participants at Time 1 (T1; M=38.4 months), 134 ASD (41 female) and 76 TD (32 female) participants at T2 (M=51.5months), 85 ASD (27 female) and 59 TD (24 female) at participants T3 (M=64.3 months), and one additional time point during middle childhood with 52 ASD (11 female) and 42 TD (17 female) participants at T4 (M=136.1 months). Due to existing evidence that disproportionate megalencephaly may represent a distinct neurophenotype in ASD, current sample and analyses did not include participants with disproportionate megalencephaly. TCV was estimated using template-based registration of T1-weighted MR images (1mm3 resolution). Primary analyses examined within-person growth in TCV during early childhood (T1-T3) using mixed level modeling; future planned analysis will examine growth of TCV into middle childhood (T1-T4). Age was separated into a within-person covariate (change in age since T1) and a between-subject covariate (starting age at T1). Mixed level models were conducted in R using lme4. Model comparisons were conducted testing interactions between sex, diagnosis, change in age. Tests of parameter estimates used Satterthwaite's degrees of freedom, as implemented in the lmerTest package.

Results: At T1, TCV was significantly enlarged in males with ASD compared to males with TD (b=+32.5cm3, t=2.78, p=.0059), but not significantly enlarged in females with ASD compared to females with TD (b=+15.6 cm3, t=1.18, p=.24). However, a significant sex by diagnosis interaction was not observed at T1 (p=.43). All groups exhibited substantial positive growth in TCV over time (Figure 1; ps ≤ 2e-16), however the rates of that growth differed by sex and diagnosis, as indicated by significant two- and three-way interactions with change in age (two-way: χ2=36.1, df=2, p=1.5e-8; three-way: χ2=4.26, df=1, p=.039). Compared to sex-matched TD controls, the rate of change in TCV was slower in ASD in both males (b=-.34 cm3/month, t=-2.49, p=.014) and females (b=-.79 cm3/month, t=-4.38, p=2.6e-5). However, the rate of growth was slowest in females with ASD (rate relative to males with ASD: b=-.69 cm3/month, t=-4.59, p=7.9e-6).

Conclusions: Brain enlargement during early childhood is not as prominent in females with ASD as in males with ASD. Moreover, females with ASD have a slower rate of TCV growth during early childhood. Future analyses will examine TCV trajectories into middle-childhood.

See more of: Neuroimaging
See more of: Neuroimaging