Associated Data
Supplementary MaterialsData Availability Statement
We first reported increased brain volume in adolescents and adults with ASD over twenty years ago5. Subsequent reports suggested that brain overgrowth in ASD may be most apparent in early childhood6–8. A study of infants at risk for ASD (33 high risk and 22 low risk), scanned from 6 to 24 months of age, found enlarged brain volume present at 12 and 24 months in the ten infants later diagnosed with autism at 24 months of age or later (mean age 32.5 months)9.
In the present study, we examined data from a subset of individuals from a longitudinal study comprising 318 infants at high familial risk for ASD (HR), of which 70 met clinical best-estimate criteria for ASD (HR-ASD) and 248 did not meet criteria for ASD (HR-neg) at 24 months of age, and 117 infants at low familial risk (LR) for ASD, who also did not meet criteria for ASD at 24 months (see Methods for diagnostic and exclusion criteria). The three groups were comparable in race/ethnicity (85% white), family income, maternal age at birth (33 years old), infant birth weight (8 lb), and gestational age at birth (39 weeks). The HR-ASD group had more males than the other two groups (83% vs. 59%) and mothers in the LR group had higher education level (Extended Data, Table 1).
Infants were evaluated at 6, 12 and 24 months of age with detailed behavioral assessments and high-resolution brain magnetic resonance imaging (MRI), to prospectively investigate brain and behavioral trajectories during infancy. The analyses described below were conducted on a subset of 106 high-risk (n = 15 HR-ASD; n=91 HR-neg) and 42 low-risk infants for whom all three MRI scans were successfully obtained. Based on our prior findings at 2 to 4 years of age2, we hypothesized that brain overgrowth in ASD begins before 24 months of age, that overgrowth is associated with hyper-expansion of cortical surface area, and that these early brain changes are temporally linked to the emergence of the defining behaviors of ASD. Finally, we sought to examine whether differences in the development of brain characteristics might suggest early biomarkers (i.e., occurring prior to the onset of the defining behaviors of ASD) for the detection of later emerging ASD.
Primary analyses examined group differences in the trajectories of brain growth rate (Figure 1). Total brain volume (TBV) growth rate did not differ between groups from 6-12 months of age. However, pairwise comparisons at 24 months showed large effect sizes for HR-ASD vs LR and HR-ASD vs HR-neg. The HR-ASD group demonstrated a significantly increased TBV growth rate in the second year compared to both the LR and HR-neg groups (Extended Data Table 2). In addition, the HR-ASD group showed a significantly increased surface area (SA) growth rate from 6 to 12 months of age compared to both the HR-neg and LR groups, with the most robust increases observed in left/right middle occipital gyrus, right cuneus and right lingual gyrus area (see Figure 2). No group differences were observed in cortical thickness (CT). We observed a significant correlation between SA growth rate from 6-12 months and enlargement in TBV at 24 months of age in all subjects (r (192) = 0.59, p <0.001), as well as the HR only subgroup (r (139) = 0.63, p < 0.001). Raw means, standard deviations, and effect size for the group comparisons of TBV and SA are provided in Extended Data (Table 3). Regional differences in SA change rate (from 6-12 months) were observed in the HR-ASD group (Figure 2).Open in a separate windowFigure 1Longitudinal trajectories of total brain volume (TBV), surface area (SA) and cortical thickness (CT) from 6 to 24 months