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